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Aβ Imaging in Aging, Alzheimer’s Disease and Other Neurodegenerative Conditions

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PET and SPECT in Neurology

Abstract

In vivo imaging of β-amyloid (Αβ) has transformed the assessment of Αβ pathology and its changes over time, extending our insight into Aβ deposition by providing highly accurate, reliable and reproducible quantitative statements of regional or global Aβ burden in the brain, essential for therapeutic trial recruitment and for the evaluation of anti-Αβ treatments. Although cross-sectional evaluation of Αβ burden does not strongly correlate with cognitive impairment in AD, it does correlate with memory impairment and a higher risk for cognitive decline in the aging population and MCI subjects. This correlation with memory impairment, one of the earliest symptoms of AD, suggests that Αβ deposition is not part of normal aging, supporting the hypothesis that Αβ deposition occurs well before the onset of symptoms. Longitudinal observations, coupled with different disease-specific biomarkers to assess potential downstream effects of Aβ, are required to confirm this hypothesis and further elucidate the role of Αβ deposition in the course of Alzheimer’s disease.

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References

  • Agdeppa ED, Kepe V, Liu J et al (2001a) Binding characteristics of radiofluorinated 6-dialkylamino-2-naphthylethylidene derivatives as positron emission tomography imaging probes for beta-amyloid plaques in Alzheimer’s disease. J Neurosci 21:RC189

    CAS  PubMed  Google Scholar 

  • Agdeppa ED, Kepe V, Shoghi-Jadid K et al (2001b) In vivo and in vitro labeling of plaques and tangles in the brain of an Alzheimer’s disease patient: a case study. J Nucl Med 42:65P

    Google Scholar 

  • Aizenstein HJ, Nebes RD, Saxton JA et al (2008) Frequent amyloid deposition without significant cognitive impairment among the elderly. Arch Neurol 65:1509–1517

    PubMed Central  PubMed  Google Scholar 

  • Albert MS, Dekosky ST, Dickson D et al (2011) The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7:270–279

    PubMed Central  PubMed  Google Scholar 

  • Apostolova LG, Hwang KS, Andrawis JP et al (2010) 3D PIB and CSF biomarker associations with hippocampal atrophy in ADNI subjects. Neurobiol Aging 31:1284–1303

    CAS  PubMed Central  PubMed  Google Scholar 

  • Archer HA, Edison P, Brooks DJ et al (2006) Amyloid load and cerebral atrophy in Alzheimer’s disease: an 11C-PIB positron emission tomography study. Ann Neurol 60:145–147

    PubMed  Google Scholar 

  • Armstrong RA, Cairns NJ, Lantos PL (2000) Beta-amyloid deposition in the temporal lobe of patients with dementia with Lewy bodies: comparison with non-demented cases and Alzheimer’s disease. Dement Geriatr Cogn Disord 11:187–192

    CAS  PubMed  Google Scholar 

  • Arnold SE, Han LY, Clark CM et al (2000) Quantitative neurohistological features of frontotemporal degeneration. Neurobiol Aging 21:913–919

    CAS  PubMed  Google Scholar 

  • Backman L, Jones S, Berger AK et al (2005) Cognitive impairment in preclinical Alzheimer’s disease: a meta-analysis. Neuropsychology 19:520–531

    PubMed  Google Scholar 

  • Bacskai BJ, Frosch MP, Freeman SH et al (2007) Molecular imaging with Pittsburgh Compound B confirmed at autopsy: a case report. Arch Neurol 64:431–434

    PubMed  Google Scholar 

  • Barrio JR, Huang SC, Cole G et al (1999) PET imaging of tangles and plaques in Alzheimer disease with a highly hydrophobic probe. J Label Compd Radiopharm 42:S194–S195

    Google Scholar 

  • Barthel H, Gertz HJ, Dresel S et al (2011) Cerebral amyloid-beta PET with florbetaben ((18)F) in patients with Alzheimer’s disease and healthy controls: a multicentre phase 2 diagnostic study. Lancet Neurol 10:424–435

    CAS  PubMed  Google Scholar 

  • Basun H, Bogdanovic N, Ingelsson M et al (2008) Clinical and neuropathological features of the arctic APP gene mutation causing early-onset alzheimer disease. Arch Neurol 65:499–505

    Google Scholar 

  • Bateman RJ, Munsell LY, Morris JC et al (2006) Human amyloid-beta synthesis and clearance rates as measured in cerebrospinal fluid in vivo. Nat Med 12:856–861

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bateman RJ, Xiong C, Benzinger TL et al (2012) Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med 367:795–804

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bauer M, Langer O, Dal-Bianco P et al (2006) A positron emission tomography microdosing study with a potential antiamyloid drug in healthy volunteers and patients with Alzheimer’s disease. Clin Pharmacol Ther 80:216–227

    CAS  PubMed  Google Scholar 

  • Beach TG, Monsell SE, Phillips LE et al (2012) Accuracy of the clinical diagnosis of Alzheimer disease at National Institute on Aging Alzheimer Disease Centers, 2005–2010. J Neuropathol Exp Neurol 71:266–273

    PubMed Central  PubMed  Google Scholar 

  • Becker JA, Hedden T, Carmasin J et al (2011) Amyloid-beta associated cortical thinning in clinically normal elderly. Ann Neurol 69:1032–1042

    CAS  PubMed Central  PubMed  Google Scholar 

  • Berg L, McKeel DW Jr, Miller JP et al (1998) Clinicopathologic studies in cognitively healthy aging and Alzheimer’s disease: relation of histologic markers to dementia severity, age, sex, and apolipoprotein E genotype. Arch Neurol 55:326–335

    CAS  PubMed  Google Scholar 

  • Blennow K, Zetterberg H, Minthon L et al (2007) Longitudinal stability of CSF biomarkers in Alzheimer’s disease. Neurosci Lett 419:18–22

    CAS  PubMed  Google Scholar 

  • Bourgeat P, Chetelat G, Villemagne VL et al (2010) Beta-amyloid burden in the temporal neocortex is related to hippocampal atrophy in elderly subjects without dementia. Neurology 74:121–127

    CAS  PubMed  Google Scholar 

  • Braak H, Braak E (1997) Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiol Aging 18:351–357

    CAS  PubMed  Google Scholar 

  • Bresjanac M, Smid LM, Vovko TD et al (2003) Molecular-imaging probe 2-(1-[6-[(2-fluoroethyl)(methyl) amino]-2-naphthyl]ethylidene) malononitrile labels prion plaques in vitro. J Neurosci 23:8029–8033

    CAS  PubMed  Google Scholar 

  • Buckley C, Ikonomovic M, Smith A et al (2012) Flutemetamol F 18 injection PET images reflect brain beta-amyloid levels. Alzheimers Dement 8:P90

    Google Scholar 

  • Buckner RL, Snyder AZ, Shannon BJ et al (2005) Molecular, structural, and functional characterization of Alzheimer’s disease: evidence for a relationship between default activity, amyloid, and memory. J Neurosci 25:7709–7717

    CAS  PubMed  Google Scholar 

  • Buckner RL, Andrews-Hanna JR, Schacter DL (2008) The brain’s default network: anatomy, function, and relevance to disease. Ann N Y Acad Sci 1124:1–38

    PubMed  Google Scholar 

  • Burack MA, Hartlein J, Flores HP et al (2010) In vivo amyloid imaging in autopsy-confirmed Parkinson disease with dementia. Neurology 74:77–84

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cairns NJ, Bigio EH, Mackenzie IR et al (2007) Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the consortium for frontotemporal lobar degeneration. Acta Neuropathol 114:5–22

    PubMed Central  PubMed  Google Scholar 

  • Cairns NJ, Ikonomovic MD, Benzinger T et al (2009) Absence of Pittsburgh Compound B detection of cerebral amyloid beta in a patient with clinical, cognitive, and cerebrospinal fluid markers of Alzheimer disease: a case report. Arch Neurol 66:1557–1562

    PubMed Central  PubMed  Google Scholar 

  • Camus V, Payoux P, Barre L et al (2012) Using PET with (18)F-AV-45 (florbetapir) to quantify brain amyloid load in a clinical environment. Eur J Nucl Med Mol Imaging 39:621–631

    Google Scholar 

  • Cappai R, White AR (1999) Amyloid beta. Int J Biochem Cell Biol 31:885–889

    CAS  PubMed  Google Scholar 

  • Carter SF, Scholl M, Almkvist O et al (2012) Evidence for astrocytosis in prodromal Alzheimer disease provided by 11C-deuterium-L-deprenyl: a multitracer PET paradigm combining 11C-Pittsburgh Compound B and 18F-FDG. J Nucl Med 53:37–46

    CAS  PubMed  Google Scholar 

  • Chang CY, Silverman DH (2004) Accuracy of early diagnosis and its impact on the management and course of Alzheimer’s disease. Expert Rev Mol Diagn 4:63–69

    PubMed  Google Scholar 

  • Chetelat G, Desgranges B, de la Sayette V et al (2003) Dissociating atrophy and hypometabolism impact on episodic memory in mild cognitive impairment. Brain 126:1955–1967

    PubMed  Google Scholar 

  • Chetelat G, Eustache F, Viader F et al (2005) FDG-PET measurement is more accurate than neuropsychological assessments to predict global cognitive deterioration in patients with mild cognitive impairment. Neurocase 11:14–25

    PubMed  Google Scholar 

  • Chetelat G, Villemagne VL, Bourgeat P et al (2010a) Relationship between atrophy and beta-amyloid deposition in Alzheimer disease. Ann Neurol 67:317–324

    CAS  PubMed  Google Scholar 

  • Chetelat G, Villemagne VL, Pike KE et al (2010b) Larger temporal volume in elderly with high versus low beta-amyloid deposition. Brain 133:3349–3358

    PubMed  Google Scholar 

  • Chetelat G, Villemagne VL, Villain N et al (2012) Accelerated cortical atrophy in cognitively normal elderly with high beta-amyloid deposition. Neurology 78:477–484

    CAS  PubMed  Google Scholar 

  • Choi SR, Golding G, Zhuang Z et al (2009) Preclinical properties of 18F-AV-45: a PET agent for Abeta plaques in the brain. J Nucl Med 50:1887–1894

    CAS  PubMed Central  PubMed  Google Scholar 

  • Clark CM, Davatzikos C, Borthakur A et al (2008) Biomarkers for early detection of Alzheimer pathology. Neurosignals 16:11–18

    CAS  PubMed Central  PubMed  Google Scholar 

  • Clark CM, Schneider JA, Bedell BJ et al (2011) Use of florbetapir-PET for imaging beta-amyloid pathology. JAMA 305:275–283

    CAS  PubMed  Google Scholar 

  • Clark CM, Pontecorvo MJ, Beach TG et al (2012) Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-beta plaques: a prospective cohort study. Lancet Neurol 11:669–678

    CAS  PubMed  Google Scholar 

  • Cohen AD, Price JC, Weissfeld LA et al (2009) Basal cerebral metabolism may modulate the cognitive effects of Abeta in mild cognitive impairment: an example of brain reserve. J Neurosci 29:14770–14778

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cohen AD, Rabinovici GD, Mathis CA et al (2012) Using Pittsburgh Compound B for in vivo PET imaging of fibrillar amyloid-beta. Adv Pharmacol 64:27–81

    CAS  PubMed Central  PubMed  Google Scholar 

  • Coleman RE (2005) Positron emission tomography diagnosis of Alzheimer’s disease. Neuroimaging Clin N Am 15:837–846, x

    PubMed  Google Scholar 

  • Cordonnier C (2010) Brain microbleeds. Pract Neurol 10:94–100

    PubMed  Google Scholar 

  • Cselenyi Z, Jonhagen ME, Forsberg A et al (2012) Clinical validation of 18F-AZD4694, an amyloid-beta-specific PET radioligand. J Nucl Med 53:415–424

    CAS  PubMed  Google Scholar 

  • Cummings JL, Vinters HV, Cole GM et al (1998) Alzheimer’s disease: etiologies, pathophysiology, cognitive reserve, and treatment opportunities. Neurology 51:S2–S17; discussion S65–S17

    CAS  PubMed  Google Scholar 

  • Davies L, Wolska B, Hilbich C et al (1988) A4 amyloid protein deposition and the diagnosis of Alzheimer’s disease: prevalence in aged brains determined by immunocytochemistry compared with conventional neuropathologic techniques. Neurology 38:1688–1693

    CAS  PubMed  Google Scholar 

  • de Leon MJ, DeSanti S, Zinkowski R et al (2006) Longitudinal CSF and MRI biomarkers improve the diagnosis of mild cognitive impairment. Neurobiol Aging 27:394–401

    PubMed  Google Scholar 

  • de Leon MJ, Mosconi L, Blennow K et al (2007) Imaging and CSF studies in the preclinical diagnosis of Alzheimer’s disease. Ann N Y Acad Sci 1097:114–145

    PubMed  Google Scholar 

  • DeKosky ST, Ikonomovic MD, Styren SD et al (2002) Upregulation of choline acetyltransferase activity in hippocampus and frontal cortex of elderly subjects with mild cognitive impairment. Ann Neurol 51:145–155

    CAS  PubMed  Google Scholar 

  • Deshpande A, Mina E, Glabe C et al (2006) Different conformations of amyloid beta induce neurotoxicity by distinct mechanisms in human cortical neurons. J Neurosci 26:6011–6018

    CAS  PubMed  Google Scholar 

  • Devanand DP, Jacobs DM, Tang MX et al (1997) The course of psychopathologic features in mild to moderate Alzheimer disease. Arch Gen Psychiatry 54:257–263

    CAS  PubMed  Google Scholar 

  • Dhollander I, Nelissen N, Van Laere K et al (2011) In vivo amyloid imaging in cortical superficial siderosis. J Neurol Neurosurg Psychiatry 82:469–471

    PubMed  Google Scholar 

  • Dierksen GA, Skehan ME, Khan MA et al (2010) Spatial relation between microbleeds and amyloid deposits in amyloid angiopathy. Ann Neurol 68:545–548

    PubMed Central  PubMed  Google Scholar 

  • Doraiswamy PM, Sperling RA, Coleman RE et al (2012) Amyloid-beta assessed by florbetapir F 18 PET and 18-month cognitive decline: a multicenter study. Neurology 79:1636–1644

    Google Scholar 

  • Drago V, Babiloni C, Bartres-Faz D et al (2011) Disease tracking markers for Alzheimer’s disease at the prodromal (MCI) stage. J Alzheimers Dis 26(Suppl 3):159–199

    PubMed  Google Scholar 

  • Driscoll I, Zhou Y, An Y et al (2011) Lack of association between (11)C-PiB and longitudinal brain atrophy in non-demented older individuals. Neurobiol Aging 32:2123–2130

    Google Scholar 

  • Drzezga A (2010) Amyloid-plaque imaging in early and differential diagnosis of dementia. Ann Nucl Med 24:55–66

    Google Scholar 

  • Drzezga A, Lautenschlager N, Siebner H et al (2003) Cerebral metabolic changes accompanying conversion of mild cognitive impairment into Alzheimer’s disease: a PET follow-up study. Eur J Nucl Med Mol Imaging 30:1104–1113

    PubMed  Google Scholar 

  • Drzezga A, Grimmer T, Riemenschneider M et al (2005) Prediction of individual clinical outcome in MCI by means of genetic assessment and (18)F-FDG PET. J Nucl Med 46:1625–1632

    CAS  PubMed  Google Scholar 

  • Drzezga A, Grimmer T, Henriksen G et al (2008) Imaging of amyloid plaques and cerebral glucose metabolism in semantic dementia and Alzheimer’s disease. Neuroimage 39:619–633

    PubMed  Google Scholar 

  • Drzezga A, Becker JA, Van Dijk KR et al (2011) Neuronal dysfunction and disconnection of cortical hubs in non-demented subjects with elevated amyloid burden. Brain 134:1635–1646

    PubMed Central  PubMed  Google Scholar 

  • Dubois B, Feldman HH, Jacova C et al (2010) Revising the definition of Alzheimer’s disease: a new lexicon. Lancet Neurol 9:1118–1127

    PubMed  Google Scholar 

  • Eckert A, Keil U, Marques CA et al (2003) Mitochondrial dysfunction, apoptotic cell death, and Alzheimer’s disease. Biochem Pharmacol 66:1627–1634

    CAS  PubMed  Google Scholar 

  • Edison P, Archer HA, Hinz R et al (2007) Amyloid, hypometabolism, and cognition in Alzheimer disease: an [11C]PIB and [18F]FDG PET study. Neurology 68:501–508

    CAS  PubMed  Google Scholar 

  • Edison P, Archer HA, Gerhard A et al (2008a) Microglia, amyloid, and cognition in Alzheimer’s disease: an [11C](R)PK11195-PET and [11C]PIB-PET study. Neurobiol Dis 32:412–419

    CAS  PubMed  Google Scholar 

  • Edison P, Rowe CC, Rinne JO et al (2008b) Amyloid load in Parkinson’s disease dementia and Lewy body dementia measured with [11C]PIB positron emission tomography. J Neurol Neurosurg Psychiatry 79:1331–1338

    CAS  PubMed  Google Scholar 

  • Engler H, Forsberg A, Almkvist O et al (2006) Two-year follow-up of amyloid deposition in patients with Alzheimer’s disease. Brain 129:2856–2866

    PubMed  Google Scholar 

  • Engler H, Santillo AF, Wang SX et al (2008) In vivo amyloid imaging with PET in frontotemporal dementia. Eur J Nucl Med Mol Imaging 35:100–106

    PubMed  Google Scholar 

  • Fagan AM, Holtzman DM (2010) Cerebrospinal fluid biomarkers of Alzheimer’s disease. Biomark Med 4:51–63

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fagan AM, Mintun MA, Mach RH et al (2006) Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta(42) in humans. Ann Neurol 59:512–519

    CAS  PubMed  Google Scholar 

  • Fagan AM, Roe CM, Xiong C et al (2007) Cerebrospinal fluid tau/beta-amyloid(42) ratio as a prediction of cognitive decline in nondemented older adults. Arch Neurol 64:343–349

    PubMed  Google Scholar 

  • Fagan AM, Mintun MA, Shah AR et al (2009) Cerebrospinal fluid tau and ptau(181) increase with cortical amyloid deposition in cognitively normal individuals: implications for future clinical trials of Alzheimer’s disease. EMBO Mol Med 1:371–380

    CAS  PubMed Central  PubMed  Google Scholar 

  • Farrer LA, Cupples LA, Haines JL et al (1997) Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer disease meta analysis consortium. JAMA 278:1349–1356

    CAS  PubMed  Google Scholar 

  • Feldman HH, Maia LF, Mackenzie IR et al (2008) Superficial siderosis: a potential diagnostic marker of cerebral amyloid angiopathy in Alzheimer disease. Stroke 39:2894–2897

    PubMed  Google Scholar 

  • Fleisher AS, Chen K, Liu X et al (2011) Using positron emission tomography and florbetapir F18 to image cortical amyloid in patients with mild cognitive impairment or dementia due to Alzheimer disease. Arch Neurol 68:1404–1411

    PubMed  Google Scholar 

  • Fodero-Tavoletti MT, Smith DP, McLean CA et al (2007) In vitro characterization of Pittsburgh Compound-B binding to Lewy bodies. J Neurosci 27:10365–10371

    CAS  PubMed  Google Scholar 

  • Fodero-Tavoletti MT, Mulligan RS, Okamura N et al (2009a) In vitro characterisation of BF227 binding to alpha-synuclein/Lewy bodies. Eur J Pharmacol 617:54–58

    CAS  PubMed  Google Scholar 

  • Fodero-Tavoletti MT, Rowe CC, McLean CA et al (2009b) Characterization of PiB binding to white matter in Alzheimer disease and other dementias. J Nucl Med 50:198–204

    PubMed  Google Scholar 

  • Fodero-Tavoletti MT, Okamura N, Furumoto S et al (2011) 18F-THK523: a novel in vivo tau imaging ligand for Alzheimer’s disease. Brain 134:1089–1100

    PubMed  Google Scholar 

  • Fodero-Tavoletti MT, Brockschnieder D, Villemagne VL et al (2012) In vitro characterisation of [18F]–florbetaben, an Aβ imaging radiotracer. Nucl Med Biol 39:1042–1048. doi:10.1016/j.nucmedbio.2012.1003.1001

  • Formaglio M, Costes N, Seguin J et al (2011) In vivo demonstration of amyloid burden in posterior cortical atrophy: a case series with PET and CSF findings. J Neurol 258:1841–1851

    PubMed  Google Scholar 

  • Forman MS, Mufson EJ, Leurgans S et al (2007) Cortical biochemistry in MCI and Alzheimer disease: lack of correlation with clinical diagnosis. Neurology 68:757–763

    CAS  PubMed  Google Scholar 

  • Forsberg A, Engler H, Almkvist O et al (2008) PET imaging of amyloid deposition in patients with mild cognitive impairment. Neurobiol Aging 29:1456–1465

    CAS  PubMed  Google Scholar 

  • Forsberg A, Almkvist O, Engler H et al (2010) High PIB retention in Alzheimer’s disease is an early event with complex relationship with CSF biomarkers and functional parameters. Curr Alzheimer Res 7:56–66

    CAS  PubMed  Google Scholar 

  • Forster S, Grimmer T, Miederer I et al (2012) Regional expansion of hypometabolism in Alzheimer’s disease follows amyloid deposition with temporal delay. Biol Psychiatry 71:792–797

    Google Scholar 

  • Foster ER, Campbell MC, Burack MA et al (2010) Amyloid imaging of Lewy body-associated disorders. Mov Disord 25:2516–2523

    PubMed Central  PubMed  Google Scholar 

  • Frisoni GB, Fox NC, Jack CR Jr et al (2010) The clinical use of structural MRI in Alzheimer disease. Nat Rev Neurol 6:67–77

    PubMed Central  PubMed  Google Scholar 

  • Furst AJ, Rabinovici GD, Rostomian AH et al (2012) Cognition, glucose metabolism and amyloid burden in Alzheimer’s disease. Neurobiol Aging 33(2):215–225

    CAS  PubMed Central  PubMed  Google Scholar 

  • Furukawa K, Okamura N, Tashiro K et al (2011) PET imaging with BF-227 in dementia with Lewy bodies. Alzheimers Dement 7:S12–S13

    Google Scholar 

  • Gomez-Isla T, West HL, Rebeck GW et al (1996) Clinical and pathological correlates of apolipoprotein E epsilon 4 in Alzheimer’s disease. Ann Neurol 39:62–70

    CAS  PubMed  Google Scholar 

  • Gomperts SN, Rentz DM, Moran E et al (2008) Imaging amyloid deposition in Lewy body diseases. Neurology 71:903–910

    CAS  PubMed Central  PubMed  Google Scholar 

  • Grimmer T, Riemenschneider M, Forstl H et al (2009) Beta amyloid in Alzheimer’s disease: increased deposition in brain is reflected in reduced concentration in cerebrospinal fluid. Biol Psychiatry 65:927–934

    CAS  PubMed Central  PubMed  Google Scholar 

  • Grimmer T, Tholen S, Yousefi BH et al (2010) Progression of cerebral amyloid load is associated with the apolipoprotein E epsilon4 genotype in Alzheimer’s disease. Biol Psychiatry 68:879–884

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gurol ME, Dierksen G, Betensky R et al (2012) Predicting sites of new hemorrhage with amyloid imaging in cerebral amyloid angiopathy. Neurology 79:320–326

    CAS  PubMed Central  PubMed  Google Scholar 

  • Halliday G, Hely M, Reid W et al (2008) The progression of pathology in longitudinally followed patients with Parkinson’s disease. Acta Neuropathol 115:409–415

    PubMed  Google Scholar 

  • Hampel H, Blennow K, Shaw LM et al (2010) Total and phosphorylated tau protein as biological markers of Alzheimer’s disease. Exp Gerontol 45:30–40

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hansson O, Zetterberg H, Buchhave P et al (2007) Prediction of Alzheimer’s disease using the CSF Abeta42/Abeta40 ratio in patients with mild cognitive impairment. Dement Geriatr Cogn Disord 23:316–320

    CAS  PubMed  Google Scholar 

  • Hardy J (1997) Amyloid, the presenilins and Alzheimer’s disease. Trends Neurosci 20:154–159

    CAS  PubMed  Google Scholar 

  • Herholz K (1995) FDG PET and differential diagnosis of dementia. Alzheimer Dis Assoc Disord 9:6–16

    CAS  PubMed  Google Scholar 

  • Hill AF, Joiner S, Wadsworth JD et al (2003) Molecular classification of sporadic Creutzfeldt-Jakob disease. Brain 126:1333–1346

    PubMed  Google Scholar 

  • Hodges JR, Patterson K (2007) Semantic dementia: a unique clinicopathological syndrome. Lancet Neurol 6:1004–1014

    CAS  PubMed  Google Scholar 

  • Hyman BT (2011) Amyloid-dependent and amyloid-independent stages of Alzheimer disease. Arch Neurol 68:1062–1064

    PubMed  Google Scholar 

  • Ikonomovic MD, Abrahamson EE, Isanski BA et al (2007) Superior frontal cortex cholinergic axon density in mild cognitive impairment and early Alzheimer disease. Arch Neurol 64:1312–1317

    PubMed  Google Scholar 

  • Ikonomovic MD, Klunk WE, Abrahamson EE et al (2008) Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease. Brain 131:1630–1645

    PubMed Central  PubMed  Google Scholar 

  • Ikonomovic MD, Klunk WE, Abrahamson EE et al (2011) Precuneus amyloid burden is associated with reduced cholinergic activity in Alzheimer disease. Neurology 77:39–47

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ikonomovic MD, Abrahamson EE, Price JC et al (2012) Early AD pathology in a [C-11]PiB-negative case: a PiB-amyloid imaging, biochemical, and immunohistochemical study. Acta Neuropathol 123:433–447

    CAS  PubMed Central  PubMed  Google Scholar 

  • Inayathullah M, Teplow DB (2011) Structural dynamics of the DeltaE22 (Osaka) familial Alzheimer’s disease-linked amyloid beta-protein. Amyloid 18:98–107

    CAS  PubMed Central  PubMed  Google Scholar 

  • Isacson O, Seo H, Lin L et al (2002) Alzheimer’s disease and Down’s syndrome: roles of APP, trophic factors and ACh. Trends Neurosci 25:79–84

    CAS  PubMed  Google Scholar 

  • Jack CR Jr, Lowe VJ, Senjem ML et al (2008a) 11C PiB and structural MRI provide complementary information in imaging of Alzheimer’s disease and amnestic mild cognitive impairment. Brain 131:665–680

    PubMed Central  PubMed  Google Scholar 

  • Jack CR Jr, Weigand SD, Shiung MM et al (2008b) Atrophy rates accelerate in amnestic mild cognitive impairment. Neurology 70:1740–1752

    PubMed Central  PubMed  Google Scholar 

  • Jack CR Jr, Lowe VJ, Weigand SD et al (2009) Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer’s disease: implications for sequence of pathological events in Alzheimer’s disease. Brain 132:1355–1365

    PubMed Central  PubMed  Google Scholar 

  • Jack CR Jr, Knopman DS, Jagust WJ et al (2010) Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurol 9:119–128

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jagust W (2009) Mapping brain beta-amyloid. Curr Opin Neurol 22:356–361

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jagust WJ (2011) Amyloid imaging: liberal or conservative? Let the data decide. Arch Neurol 68:1377–1378

    PubMed  Google Scholar 

  • Jagust W, Reed B, Mungas D et al (2007) What does fluorodeoxyglucose PET imaging add to a clinical diagnosis of dementia? Neurology 69:871–877

    CAS  PubMed  Google Scholar 

  • Jellinger K (1990) Morphology of Alzheimer disease and related disorders. In: Maurer K et al (eds) Alzheimer disease: epidemiology, neuropathology, neurochemistry, and clinics. Springer, Berlin, pp 61–77

    Google Scholar 

  • Jellinger KA (2010) Con: can neuropathology really confirm the exact diagnosis? Alzheimers Res Ther 2:11

    PubMed Central  PubMed  Google Scholar 

  • Jellinger KA, Attems J (2005) Prevalence and pathogenic role of cerebrovascular lesions in Alzheimer disease. J Neurol Sci 229–230:37–41

    PubMed  Google Scholar 

  • Jellinger KA, Bancher C (1998) Neuropathology of Alzheimer’s disease: a critical update. J Neural Transm Suppl 54:77–95

    CAS  PubMed  Google Scholar 

  • Johansson A, Savitcheva I, Forsberg A et al (2008) [(11)C]-PIB imaging in patients with Parkinson’s disease: preliminary results. Parkinsonism Relat Disord 14:345–347

    CAS  PubMed  Google Scholar 

  • Johnson KA (2006) Amyloid imaging of Alzheimer’s disease using Pittsburgh Compound B. Curr Neurol Neurosci Rep 6:496–503

    PubMed  Google Scholar 

  • Johnson N, Davis T, Bosanquet N (2000) The epidemic of Alzheimer’s disease. How can we manage the costs? Pharmacoeconomics 18:215–223

    CAS  PubMed  Google Scholar 

  • Johnson KA, Gregas M, Becker JA et al (2007) Imaging of amyloid burden and distribution in cerebral amyloid angiopathy. Ann Neurol 62:229–234

    PubMed  Google Scholar 

  • Johnson AE, Jeppsson F, Sandell J et al (2009) AZD2184: a radioligand for sensitive detection of beta-amyloid deposits. J Neurochem 108:1177–1186

    CAS  PubMed  Google Scholar 

  • Josephs KA, Holton JL, Rossor MN et al (2004) Frontotemporal lobar degeneration and ubiquitin immunohistochemistry. Neuropathol Appl Neurobiol 30:369–373

    CAS  PubMed  Google Scholar 

  • Jureus A, Swahn BM, Sandell J et al (2010) Characterization of AZD4694, a novel fluorinated Abeta plaque neuroimaging PET radioligand. J Neurochem 114:784–794

    CAS  PubMed  Google Scholar 

  • Kadir A, Marutle A, Gonzalez D et al (2011) Positron emission tomography imaging and clinical progression in relation to molecular pathology in the first Pittsburgh Compound B positron emission tomography patient with Alzheimer’s disease. Brain 134:301–317

    PubMed Central  PubMed  Google Scholar 

  • Kalaitzakis ME, Walls AJ, Pearce RK et al (2011) Striatal Abeta peptide deposition mirrors dementia and differentiates DLB and PDD from other parkinsonian syndromes. Neurobiol Dis 41:377–384

    CAS  PubMed  Google Scholar 

  • Kambe T, Motoi Y, Ishii K et al (2010) Posterior cortical atrophy with [11C] Pittsburgh Compound B accumulation in the primary visual cortex. J Neurol 257:469–471

    PubMed  Google Scholar 

  • Karran E, Mercken M, De Strooper B (2011) The amyloid cascade hypothesis for Alzheimer’s disease: an appraisal for the development of therapeutics. Nat Rev Drug Discov 10:698–712

    CAS  PubMed  Google Scholar 

  • Kemppainen NM, Aalto S, Wilson IA et al (2007) PET amyloid ligand [11C]PIB uptake is increased in mild cognitive impairment. Neurology 68:1603–1606

    CAS  PubMed  Google Scholar 

  • Kemppainen NM, Aalto S, Karrasch M et al (2008) Cognitive reserve hypothesis: Pittsburgh Compound B and fluorodeoxyglucose positron emission tomography in relation to education in mild Alzheimer’s disease. Ann Neurol 63:112–118

    PubMed  Google Scholar 

  • Kennedy AM, Frackowiak RS, Newman SK et al (1995) Deficits in cerebral glucose metabolism demonstrated by positron emission tomography in individuals at risk of familial Alzheimer’s disease. Neurosci Lett 186:17–20

    CAS  PubMed  Google Scholar 

  • Khachaturian ZS (1985) Diagnosis of Alzheimer’s disease. Arch Neurol 42:1097–1105

    CAS  PubMed  Google Scholar 

  • Kikuchi A, Takeda A, Okamura N et al (2010) In vivo visualization of alpha-synuclein deposition by carbon-11-labelled 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy]benzoxazole positron emission tomography in multiple system atrophy. Brain 133:1772–1778

    PubMed  Google Scholar 

  • Klunk WE (2011) Amyloid imaging as a biomarker for cerebral beta-amyloidosis and risk prediction for Alzheimer dementia. Neurobiol Aging 32(Suppl 1):S20–S36

    CAS  PubMed Central  PubMed  Google Scholar 

  • Klunk WE, Wang Y, Huang GF et al (2001) Uncharged thioflavin-T derivatives bind to amyloid-beta protein with high affinity and readily enter the brain. Life Sci 69:1471–1484

    CAS  PubMed  Google Scholar 

  • Klunk WE, Wang Y, Huang GF et al (2003) The binding of 2-(4'-methylaminophenyl)benzothiazole to postmortem brain homogenates is dominated by the amyloid component. J Neurosci 23:2086–2092

    CAS  PubMed  Google Scholar 

  • Klunk WE, Engler H, Nordberg A et al (2004) Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol 55:306–319

    CAS  PubMed  Google Scholar 

  • Klunk WE, Lopresti BJ, Ikonomovic MD et al (2005) Binding of the positron emission tomography tracer Pittsburgh Compound-B reflects the amount of amyloid-beta in Alzheimer’s disease brain but not in transgenic mouse brain. J Neurosci 25:10598–10606

    CAS  PubMed  Google Scholar 

  • Klunk WE, Price JC, Mathis CA et al (2007) Amyloid deposition begins in the striatum of presenilin-1 mutation carriers from two unrelated pedigrees. J Neurosci 27:6174–6184

    CAS  PubMed Central  PubMed  Google Scholar 

  • Klunk W, Cohen AD, Bi W et al (2012) Why we need two cutoffs for amyloid imaging: early versus Alzheimer’s-like amyloid-positivity. Alzheimers Dement 8:P453–P454

    Google Scholar 

  • Knudsen KA, Rosand J, Karluk D et al (2001) Clinical diagnosis of cerebral amyloid angiopathy: validation of the Boston criteria. Neurology 56:537–539

    CAS  PubMed  Google Scholar 

  • Koeppe RA, Gilman S, Junck L et al (2008) Differentiating Alzheimer’s disease from dementia with Lewy bodies and Parkinson’s disease with (+)-[11C]dihydrotetrabenazine positron emission tomography. Alzheimers Dement 4:S67–S76

    PubMed  Google Scholar 

  • Koivunen J, Pirttila T, Kemppainen N et al (2008a) PET amyloid ligand [C]PIB uptake and cerebrospinal fluid beta-amyloid in mild cognitive impairment. Dement Geriatr Cogn Disord 26:378–383

    CAS  PubMed  Google Scholar 

  • Koivunen J, Verkkoniemi A, Aalto S et al (2008b) PET amyloid ligand [11C]PIB uptake shows predominantly striatal increase in variant Alzheimer’s disease. Brain 131:1845–1853

    CAS  PubMed  Google Scholar 

  • Kuczynski B, Reed B, Mungas D et al (2008) Cognitive and anatomic contributions of metabolic decline in Alzheimer disease and cerebrovascular disease. Arch Neurol 65:650–655

    PubMed Central  PubMed  Google Scholar 

  • Kudo Y (2006) Development of amyloid imaging PET probes for an early diagnosis of Alzheimer’s disease. Minim Invasive Ther Allied Technol 15:209–213

    PubMed  Google Scholar 

  • Kudo Y, Okamura N, Furumoto S et al (2007) 2-(2-[2-Dimethylaminothiazol-5-yl]Ethenyl)-6- (2-[Fluoro]Ethoxy)Benzoxazole: a novel PET agent for in vivo detection of dense amyloid plaques in Alzheimer’s disease patients. J Nucl Med 48:553–561

    CAS  PubMed  Google Scholar 

  • Landau SM, Harvey D, Madison CM et al (2011) Associations between cognitive, functional, and FDG-PET measures of decline in AD and MCI. Neurobiol Aging 32(7):1207–1218

    PubMed Central  PubMed  Google Scholar 

  • Landt J, D’Abrera JC, Holland AJ et al (2011) Using positron emission tomography and carbon 11-labeled Pittsburgh Compound B to image brain fibrillar beta-amyloid in adults with Down syndrome: safety, acceptability, and feasibility. Arch Neurol 68:890–896

    PubMed  Google Scholar 

  • Larson EB, Edwards JK, O’Meara E et al (1996) Neuropathologic diagnostic outcomes from a cohort of outpatients with suspected dementia. J Gerontol A Biol Sci Med Sci 51(suppl 6):M313–M318

    CAS  PubMed  Google Scholar 

  • Laruelle M, Slifstein M, Huang Y (2003) Relationships between radiotracer properties and image quality in molecular imaging of the brain with positron emission tomography. Mol Imaging Biol 5:363–375

    PubMed  Google Scholar 

  • Leinonen V, Alafuzoff I, Aalto S et al (2008) Assessment of beta-amyloid in a frontal cortical brain biopsy specimen and by positron emission tomography with carbon 11-labeled Pittsburgh Compound B. Arch Neurol 65:1304–1309

    PubMed  Google Scholar 

  • Leuner K, Hauptmann S, Abdel-Kader R et al (2007) Mitochondrial dysfunction: the first domino in brain aging and Alzheimer’s disease? Antioxid Redox Signal 9:1659–1675

    CAS  PubMed  Google Scholar 

  • LeVine H 3rd (1999) Quantification of beta-sheet amyloid fibril structures with thioflavin T. Methods Enzymol 309:274–284

    CAS  PubMed  Google Scholar 

  • Levine H 3rd, Walker LC (2010a) Molecular polymorphism of Abeta in Alzheimer’s disease. Neurobiol Aging 31(4):542–548

    CAS  PubMed Central  PubMed  Google Scholar 

  • Levine H 3rd, Walker LC (2010b) Molecular polymorphism of Abeta in Alzheimer’s disease. Neurobiol Aging 31:542–548

    CAS  PubMed Central  PubMed  Google Scholar 

  • Leyton CE, Villemagne VL, Savage S et al (2011) Subtypes of progressive aphasia: application of the international consensus criteria and validation using {beta}-amyloid imaging. Brain 134:3030–3043

    Google Scholar 

  • Liberski PP (2004) Amyloid plaques in transmissible spongiform encephalopathies (prion diseases). Folia Neuropathol 42(Suppl B):109–119

    PubMed  Google Scholar 

  • Lin KS, Debnath ML, Mathis CA et al (2009) Synthesis and beta-amyloid binding properties of rhenium 2-phenylbenzothiazoles. Bioorg Med Chem Lett 19:2258–2262

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lister-James J, Pontecorvo MJ, Clark C et al (2011) Florbetapir f-18: a histopathologically validated beta-amyloid positron emission tomography imaging agent. Semin Nucl Med 41:300–304

    PubMed  Google Scholar 

  • Lockhart A, Ye L, Judd DB et al (2005) Evidence for the presence of three distinct binding sites for the thioflavin T class of Alzheimer’s disease PET imaging agents on beta-amyloid peptide fibrils. J Biol Chem 280:7677–7684

    CAS  PubMed  Google Scholar 

  • Lockhart A, Lamb JR, Osredkar T et al (2007) PIB is a non-specific imaging marker of amyloid-beta (Abeta) peptide-related cerebral amyloidosis. Brain 130:2607–2615

    CAS  PubMed  Google Scholar 

  • Lopresti BJ, Klunk WE, Mathis CA et al (2005) Simplified quantification of Pittsburgh Compound B amyloid imaging PET studies: a comparative analysis. J Nucl Med 46:1959–1972

    CAS  PubMed  Google Scholar 

  • Lowe VJ, Kemp BJ, Jack CR Jr et al (2009) Comparison of 18F-FDG and PiB PET in cognitive impairment. J Nucl Med 50:878–886

    PubMed Central  PubMed  Google Scholar 

  • Mackenzie IR, Foti D, Woulfe J et al (2008) Atypical frontotemporal lobar degeneration with ubiquitin-positive, TDP-43-negative neuronal inclusions. Brain 131:1282–1293

    PubMed  Google Scholar 

  • Maeda J, Ji B, Irie T et al (2007) Longitudinal, quantitative assessment of amyloid, neuroinflammation, and anti-amyloid treatment in a living mouse model of Alzheimer’s disease enabled by positron emission tomography. J Neurosci 27:10957–10968

    CAS  PubMed  Google Scholar 

  • Maetzler W, Reimold M, Liepelt I et al (2008) [11C]PIB binding in Parkinson’s disease dementia. Neuroimage 39:1027–1033

    PubMed  Google Scholar 

  • Maetzler W, Liepelt I, Reimold M et al (2009) Cortical PIB binding in Lewy body disease is associated with Alzheimer-like characteristics. Neurobiol Dis 34:107–112

    CAS  PubMed  Google Scholar 

  • Maezawa I, Hong HS, Liu R et al (2008) Congo red and thioflavin-T analogs detect Abeta oligomers. J Neurochem 104:457–468

    CAS  PubMed  Google Scholar 

  • Majocha RE, Reno JM, Friedland RP et al (1992) Development of a monoclonal antibody specific for ß/A4 amyloid in Alzheimer’s disease brain for application to in vivo imaging of amyloid angiopathy. J Nucl Med 33:2184–2189

    CAS  PubMed  Google Scholar 

  • Marchant NL, Reed BR, Decarli CS et al (2012) Cerebrovascular disease, beta-amyloid, and cognition in aging. Neurobiol Aging 33(5):1006.e25–36

    CAS  Google Scholar 

  • Maruyama M, Maeda J, Ji B et al (2009) In-vivo optical and PET detections of fibrillar tau lesions in a mouse model of tauopathies. Alzheimers Dement 55:P209–P210 [abstract]

    Google Scholar 

  • Masliah E, Rockenstein E, Veinbergs I et al (2001) Beta-amyloid peptides enhance alpha-synuclein accumulation and neuronal deficits in a transgenic mouse model linking Alzheimer’s disease and Parkinson’s disease. Proc Natl Acad Sci U S A 98:12245–12250

    CAS  PubMed Central  PubMed  Google Scholar 

  • Masters CL (2005) Neuropathology of Alzheimer’s disease. In: Burns A et al (eds) Dementia, 3rd edn. Hodder Arnold, London, pp 393–407

    Google Scholar 

  • Masters CL, Beyreuther K (2005) The neuropathology of Alzheimer’s disease in the year 2005. In: Beal MF et al (eds) Neurodegenerative diseases: neurobiology, pathogenesis and therapeutics. Cambridge University Press, Cambridge, pp 433–440

    Google Scholar 

  • Masters CL, Beyreuther K (2006) Alzheimer’s centennial legacy: prospects for rational therapeutic intervention targeting the Abeta amyloid pathway. Brain 129:2823–2839

    PubMed  Google Scholar 

  • Masters CL, Simms G, Weinman NA et al (1985) Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci U S A 82:4245–4249

    CAS  PubMed Central  PubMed  Google Scholar 

  • Masters CL, Cappai R, Barnham KJ et al (2006) Molecular mechanisms for Alzheimer’s disease: implications for neuroimaging and therapeutics. J Neurochem 97:1700–1725

    CAS  PubMed  Google Scholar 

  • Mathis CA, Bacskai BJ, Kajdasz ST et al (2002) A lipophilic thioflavin-T derivative for positron emission tomography (PET) imaging of amyloid in brain. Bioorg Med Chem Lett 12:295–298

    CAS  PubMed  Google Scholar 

  • Mathis CA, Klunk WE, Price JC et al (2005) Imaging technology for neurodegenerative diseases: progress toward detection of specific pathologies. Arch Neurol 62:196–200

    PubMed  Google Scholar 

  • Mathis CA, Lopresti BJ, Klunk WE (2007) Impact of amyloid imaging on drug development in Alzheimer’s disease. Nucl Med Biol 34:809–822

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mattsson N, Zetterberg H, Hansson O et al (2009) CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA 302:385–393

    CAS  PubMed  Google Scholar 

  • Mattsson N, Andreasson U, Persson S et al (2011) The Alzheimer’s Association external quality control program for cerebrospinal fluid biomarkers. Alzheimers Dement 7:386–395, e386

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mawuenyega KG, Sigurdson W, Ovod V et al (2010) Decreased clearance of CNS beta-amyloid in Alzheimer’s disease. Science 330:1774

    CAS  PubMed Central  PubMed  Google Scholar 

  • McKeith IG, Mosimann UP (2004) Dementia with Lewy bodies and Parkinson’s disease. Parkinsonism Relat Disord 10(Suppl 1):S15–S18

    PubMed  Google Scholar 

  • McKeith IG, Dickson DW, Lowe J et al (2005) Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 65:1863–1872

    CAS  PubMed  Google Scholar 

  • McKhann GM, Knopman DS, Chertkow H et al (2011) The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7:263–269

    PubMed Central  PubMed  Google Scholar 

  • McLean CA, Cherny RA, Fraser FW et al (1999) Soluble pool of Aß amyloid as a determinant of severity of neurodegeneration in Alzheimer’s disease. Ann Neurol 46:860–866

    CAS  PubMed  Google Scholar 

  • Michaelis ML, Dobrowsky RT, Li G (2002) Tau neurofibrillary pathology and microtubule stability. J Mol Neurosci 19:289–293

    CAS  PubMed  Google Scholar 

  • Mielke R, Herholz K, Grond M et al (1992) Differences of regional cerebral glucose metabolism between presenile and senile dementia of Alzheimer type. Neurobiol Aging 13:93–98

    CAS  PubMed  Google Scholar 

  • Mintun MA, Larossa GN, Sheline YI et al (2006) [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurology 67:446–452

    CAS  PubMed  Google Scholar 

  • Mirra SS, Heyman A, McKeel D et al (1991) The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology 41:479–486

    CAS  PubMed  Google Scholar 

  • Montine TJ, Phelps CH, Beach TG et al (2012) National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach. Acta Neuropathol 123:1–11

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mormino EC, Kluth JT, Madison CM et al (2009) Episodic memory loss is related to hippocampal-mediated beta-amyloid deposition in elderly subjects. Brain 132:1310–1323

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mormino EC, Brandel MG, Madison CM et al (2012) Not quite PIB-positive, not quite PIB-negative: slight PIB elevations in elderly normal control subjects are biologically relevant. Neuroimage 59:1152–1160

    PubMed Central  PubMed  Google Scholar 

  • Morris JC (2012) Revised criteria for mild cognitive impairment may compromise the diagnosis of Alzheimer disease dementia. Arch Neurol 69:700–708. doi:10.1001/archneurol.2011.3152

  • Morris JC, Price AL (2001) Pathologic correlates of nondemented aging, mild cognitive impairment, and early-stage Alzheimer’s disease. J Mol Neurosci 17:101–118

    CAS  PubMed  Google Scholar 

  • Morris JC, Kimberly A, Quaid K et al (2005) Role of biomarkers in studies of presymptomatic Alzheimer’s disease. Alzheimers Dement 1:145–151

    CAS  PubMed  Google Scholar 

  • Morris JC, Roe CM, Grant EA et al (2009) Pittsburgh Compound B imaging and prediction of progression from cognitive normality to symptomatic Alzheimer disease. Arch Neurol 66:1469–1475

    PubMed Central  PubMed  Google Scholar 

  • Morris JC, Roe CM, Xiong C et al (2010) APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging. Ann Neurol 67:122–131

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mortimer JA (1997) Brain reserve and the clinical expression of Alzheimer’s disease. Geriatrics 52(Suppl 2):S50–S53

    PubMed  Google Scholar 

  • Mosconi L, Perani D, Sorbi S et al (2004) MCI conversion to dementia and the APOE genotype: a prediction study with FDG-PET. Neurology 63:2332–2340

    CAS  PubMed  Google Scholar 

  • Mosconi L, De Santi S, Li Y et al (2006a) Visual rating of medial temporal lobe metabolism in mild cognitive impairment and Alzheimer’s disease using FDG-PET. Eur J Nucl Med Mol Imaging 33:210–221

    PubMed  Google Scholar 

  • Mosconi L, Sorbi S, de Leon MJ et al (2006b) Hypometabolism exceeds atrophy in presymptomatic early-onset familial Alzheimer’s disease. J Nucl Med 47:1778–1786

    CAS  PubMed  Google Scholar 

  • Mott RT, Dickson DW, Trojanowski JQ et al (2005) Neuropathologic, biochemical, and molecular characterization of the frontotemporal dementias. J Neuropathol Exp Neurol 64:420–428

    CAS  PubMed  Google Scholar 

  • Naslund J, Haroutunian V, Mohs R et al (2000) Correlation between elevated levels of amyloid beta-peptide in the brain and cognitive decline. JAMA 283:1571–1577

    CAS  PubMed  Google Scholar 

  • Nelissen N, Van Laere K, Thurfjell L et al (2009) Phase 1 study of the Pittsburgh Compound B derivative 18F-flutemetamol in healthy volunteers and patients with probable Alzheimer disease. J Nucl Med 50:1251–1259

    CAS  PubMed  Google Scholar 

  • Neumann M, Sampathu DM, Kwong LK et al (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314:130–133

    CAS  PubMed  Google Scholar 

  • Neumann M, Rademakers R, Roeber S et al (2009) A new subtype of frontotemporal lobar degeneration with FUS pathology. Brain 132:2922–2931

    PubMed Central  PubMed  Google Scholar 

  • Newberg AB, Wintering NA, Plossl K et al (2006) Safety, biodistribution, and dosimetry of 123I-IMPY: a novel amyloid plaque-imaging agent for the diagnosis of Alzheimer’s disease. J Nucl Med 47:748–754

    CAS  PubMed  Google Scholar 

  • Ng S, Villemagne VL, Berlangieri S et al (2007a) Visual assessment versus quantitative assessment of 11C-PIB PET and 18F-FDG PET for detection of Alzheimer’s disease. J Nucl Med 48:547–552

    CAS  PubMed  Google Scholar 

  • Ng SY, Villemagne VL, Masters CL et al (2007b) Evaluating atypical dementia syndromes using positron emission tomography with carbon 11 labeled Pittsburgh Compound B. Arch Neurol 64:1140–1144

    PubMed  Google Scholar 

  • Noda A, Murakami Y, Nishiyama S et al (2008) Amyloid imaging in aged and young macaques with [11C]PIB and [18F]FDDNP. Synapse 62:472–475

    CAS  PubMed  Google Scholar 

  • Nordberg A (2004) PET imaging of amyloid in Alzheimer’s disease. Lancet Neurol 3:519–527

    CAS  PubMed  Google Scholar 

  • Nordberg A (2007) Amyloid imaging in Alzheimer’s disease. Curr Opin Neurol 20:398–402

    CAS  PubMed  Google Scholar 

  • Nyberg S, Jonhagen ME, Cselenyi Z et al (2009) Detection of amyloid in Alzheimer’s disease with positron emission tomography using [11C]AZD2184. Eur J Nucl Med Mol Imaging 36:1859–1863

    PubMed Central  PubMed  Google Scholar 

  • O’Brien J, Ames D, Burns A (2000) Dementia, 2nd edn. Arnold, London

    Google Scholar 

  • O’Brien JT, Colloby S, Fenwick J et al (2004) Dopamine transporter loss visualized with FP-CIT SPECT in the differential diagnosis of dementia with Lewy bodies. Arch Neurol 61:919–925

    PubMed  Google Scholar 

  • Ojida A, Sakamoto T, Inoue MA et al (2009) Fluorescent BODIPY-based Zn(II) complex as a molecular probe for selective detection of neurofibrillary tangles in the brains of Alzheimer’s disease patients. J Am Chem Soc 131:6543–6548

    CAS  PubMed  Google Scholar 

  • Okamura N, Suemoto T, Shimadzu H et al (2004) Styrylbenzoxazole derivatives for in vivo imaging of amyloid plaques in the brain. J Neurosci 24:2535–2541

    CAS  PubMed  Google Scholar 

  • Okamura N, Suemoto T, Furumoto S et al (2005) Quinoline and benzimidazole derivatives: candidate probes for in vivo imaging of tau pathology in Alzheimer’s disease. J Neurosci 25:10857–10862

    CAS  PubMed  Google Scholar 

  • Okamura N, Shiga Y, Furumoto S et al (2010) In vivo detection of prion amyloid plaques using [(11)C]BF-227 PET. Eur J Nucl Med Mol Imaging 37:934–941

    CAS  PubMed  Google Scholar 

  • Okello A, Edison P, Archer HA et al (2009a) Microglial activation and amyloid deposition in mild cognitive impairment: a PET study. Neurology 72:56–62

    CAS  PubMed Central  PubMed  Google Scholar 

  • Okello A, Koivunen J, Edison P et al (2009b) Conversion of amyloid positive and negative MCI to AD over 3 years: an 11C-PIB PET study. Neurology 73:754–760

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ong K, Villemagne VL, Lamngon N et al (2010) Assessment of Aβ deposition in mild cognitive impairment with 18F-Florbetaben. Alzheimer Dement 6:S26

    Google Scholar 

  • Opazo C, Luza S, Villemagne VL et al (2006) Radioiodinated clioquinol as a biomarker for beta-amyloid: Zn complexes in Alzheimer’s disease. Aging Cell 5:69–79

    CAS  PubMed  Google Scholar 

  • Ossenkoppele R, van Berckel BN, Prins ND (2011) Amyloid imaging in prodromal Alzheimer’s disease. Alzheimers Res Ther 3:26

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ossenkoppele R, Tolboom N, Foster-Dingley JC et al (2012) Longitudinal imaging of Alzheimer pathology using [11C]PIB, [18F]FDDNP and [18F]FDG PET. Eur J Nucl Med Mol Imaging 39:990–1000

    CAS  PubMed  Google Scholar 

  • Ostrowitzki S, Deptula D, Thurfjell L et al (2012) Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab. Arch Neurol 69(2):198–207

    PubMed  Google Scholar 

  • Petersen RC (2000) Mild cognitive impairment: transition between aging and Alzheimer’s disease. Neurologia 15:93–101

    CAS  PubMed  Google Scholar 

  • Petersen RC, Smith GE, Ivnik RJ et al (1995) Apolipoprotein E status as a predictor of the development of Alzheimer’s disease in memory-impaired individuals. JAMA 273:1274–1278

    CAS  PubMed  Google Scholar 

  • Petersen RC, Smith GE, Waring SC et al (1999) Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 56:303–308

    CAS  PubMed  Google Scholar 

  • Pettersen JA, Sathiyamoorthy G, Gao FQ et al (2008) Microbleed topography, leukoaraiosis, and cognition in probable Alzheimer disease from the Sunnybrook dementia study. Arch Neurol 65:790–795

    PubMed  Google Scholar 

  • Phelps ME (2000) PET: the merging of biology and imaging into molecular imaging. J Nucl Med 41:661–681

    CAS  PubMed  Google Scholar 

  • Pike VW (2009) PET radiotracers: crossing the blood-brain barrier and surviving metabolism. Trends Pharmacol Sci 30:431–440

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pike KE, Savage G, Villemagne VL et al (2007) Beta-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer’s disease. Brain 130:2837–2844

    PubMed  Google Scholar 

  • Pike KE, Ellis KA, Villemagne VL et al (2011) Cognition and beta-amyloid in preclinical Alzheimer’s disease: data from the AIBL study. Neuropsychologia 49:2384–2390

    PubMed  Google Scholar 

  • Pletnikova O, West N, Lee MK et al (2005) Abeta deposition is associated with enhanced cortical a-synuclein lesions in Lewy body diseases. Neurobiol Aging 26:1183–1192

    Google Scholar 

  • Price JL, Morris JC (1999) Tangles and plaques in nondemented aging and “preclinical” Alzheimer’s disease. Ann Neurol 45:358–368

    CAS  PubMed  Google Scholar 

  • Price JC, Klunk WE, Lopresti BJ et al (2005) Kinetic modeling of amyloid binding in humans using PET imaging and Pittsburgh Compound-B. J Cereb Blood Flow Metab 25:1528–1547

    CAS  PubMed  Google Scholar 

  • Qiu C, Xu W, Fratiglioni L (2010) Vascular and psychosocial factors in Alzheimer’s disease: epidemiological evidence toward intervention. J Alzheimers Dis 20:689–697

    PubMed  Google Scholar 

  • Qu W, Kung MP, Hou C et al (2007a) Novel styrylpyridines as probes for SPECT imaging of amyloid plaques. J Med Chem 50:2157–2165

    CAS  PubMed  Google Scholar 

  • Qu W, Kung MP, Hou C et al (2007b) Radioiodinated aza-diphenylacetylenes as potential SPECT imaging agents for beta-amyloid plaque detection. Bioorg Med Chem Lett 17:3581–3584

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rabinovici GD, Jagust WJ (2009) Amyloid imaging in aging and dementia: testing the amyloid hypothesis in vivo. Behav Neurol 21:117–128

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rabinovici GD, Miller BL (2010) Frontotemporal lobar degeneration: epidemiology, pathophysiology, diagnosis and management. CNS Drugs 24:375–398

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rabinovici GD, Furst AJ, O’Neil JP et al (2007) 11C-PIB PET imaging in Alzheimer disease and frontotemporal lobar degeneration. Neurology 68:1205–1212

    CAS  PubMed  Google Scholar 

  • Rabinovici GD, Jagust WJ, Furst AJ et al (2008) Abeta amyloid and glucose metabolism in three variants of primary progressive aphasia. Ann Neurol 64:388–401

    PubMed Central  PubMed  Google Scholar 

  • Rabinovici GD, Furst AJ, Alkalay A et al (2010) Increased metabolic vulnerability in early-onset alzheimer’s disease is not related to amyloid burden. Brain 133:512–528

    Google Scholar 

  • Rabinovici GD, Rosen HJ, Alkalay A et al (2011) Amyloid vs FDG-PET in the differential diagnosis of AD and FTLD. Neurology 77:2034–2042

    CAS  PubMed Central  PubMed  Google Scholar 

  • Reiman EM, Caselli RJ, Yun LS et al (1996) Preclinical evidence of Alzheimer’s disease in persons homozygous for the epsilon 4 allele for apolipoprotein E. N Engl J Med 334:752–758

    CAS  PubMed  Google Scholar 

  • Reiman EM, Chen K, Liu X et al (2009) Fibrillar amyloid-β burden in cognitively normal people at 3 levels of genetic risk for Alzheimer’s disease. Proc Natl Acad Sci U S A 106:6820–6825

    CAS  PubMed Central  PubMed  Google Scholar 

  • Remes AM, Laru L, Tuominen H et al (2008) Carbon 11-labeled Pittsburgh Compound B positron emission tomographic amyloid imaging in patients with APP locus duplication. Arch Neurol 65:540–544

    PubMed  Google Scholar 

  • Rentz DM, Locascio JJ, Becker JA et al (2010) Cognition, reserve, and amyloid deposition in normal aging. Ann Neurol 67:353–364

    PubMed Central  PubMed  Google Scholar 

  • Resende R, Pereira C, Agostinho P et al (2007) Susceptibility of hippocampal neurons to Abeta peptide toxicity is associated with perturbation of Ca2+ homeostasis. Brain Res 1143:11–21

    CAS  PubMed  Google Scholar 

  • Resnick SM, Lamar M, Driscoll I (2007) Vulnerability of the orbitofrontal cortex to age-associated structural and functional brain changes. Ann N Y Acad Sci 1121:562–575

    PubMed  Google Scholar 

  • Resnick SM, Sojkova J, Zhou Y et al (2010) Longitudinal cognitive decline is associated with fibrillar amyloid-beta measured by [11C]PiB. Neurology 74:807–815

    CAS  PubMed Central  PubMed  Google Scholar 

  • Riekse RG, Leverenz JB, McCormick W et al (2004) Effect of vascular lesions on cognition in Alzheimer’s disease: a community-based study. J Am Geriatr Soc 52:1442–1448

    PubMed Central  PubMed  Google Scholar 

  • Rinne JO, Brooks DJ, Rossor MN et al (2010) 11C-PiB PET assessment of change in fibrillar amyloid-beta load in patients with Alzheimer’s disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study. Lancet Neurol 9:363–372

    CAS  PubMed  Google Scholar 

  • Roder S, Danober L, Pozza MF et al (2003) Electrophysiological studies on the hippocampus and prefrontal cortex assessing the effects of amyloidosis in amyloid precursor protein 23 transgenic mice. Neuroscience 120:705–720

    CAS  PubMed  Google Scholar 

  • Roe CM, Mintun MA, D’Angelo G et al (2008) Alzheimer disease and cognitive reserve: variation of education effect with carbon 11-labeled Pittsburgh Compound B uptake. Arch Neurol 65:1467–1471

    PubMed Central  PubMed  Google Scholar 

  • Rosen RF, Walker LC, Levine H, 3rd (2011) PIB binding in aged primate brain: enrichment of high-affinity sites in humans with Alzheimer’s disease. Neurobiol Aging 32:223–234

    Google Scholar 

  • Rosendorff C, Beeri MS, Silverman JM (2007) Cardiovascular risk factors for Alzheimer’s disease. Am J Geriatr Cardiol 16:143–149

    PubMed  Google Scholar 

  • Rossor MN, Kennedy AM, Frackowiak RS (1996) Clinical and neuroimaging features of familial Alzheimer’s disease. Ann N Y Acad Sci 777:49–56

    CAS  PubMed  Google Scholar 

  • Rowe CC, Villemagne VL (2011) Brain amyloid imaging. J Nucl Med 52:1733–1740

    CAS  PubMed  Google Scholar 

  • Rowe CC, Ng S, Ackermann U et al (2007) Imaging beta-amyloid burden in aging and dementia. Neurology 68:1718–1725

    CAS  PubMed  Google Scholar 

  • Rowe CC, Ackerman U, Browne W et al (2008) Imaging of amyloid beta in Alzheimer’s disease with (18)F-BAY94-9172, a novel PET tracer: proof of mechanism. Lancet Neurol 7:129–135

    CAS  PubMed  Google Scholar 

  • Rowe CC, Ellis KA, Rimajova M et al (2010) Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Neurobiol Aging 31:1275–1283

    PubMed  Google Scholar 

  • Sabbagh MN, Fleisher A, Chen K et al (2011) Positron emission tomography and neuropathologic estimates of fibrillar amyloid-beta in a patient with Down syndrome and Alzheimer disease. Arch Neurol 68:1461–1466

    PubMed Central  PubMed  Google Scholar 

  • Sabbagh M, Seibyl J, Akatsu H et al (2012) Multicentre phase 3 trial on florbetaben for beta-amyloid brain PET in Alzheimer’s disease. Alzheimers Dement 8:P90

    Google Scholar 

  • Sair HI, Doraiswamy PM, Petrella JR (2004) In vivo amyloid imaging in Alzheimer’s disease. Neuroradiology 46:93–104

    CAS  PubMed  Google Scholar 

  • Salmon E, Sadzot B, Maquet P et al (1994) Differential diagnosis of Alzheimer’s disease with PET. J Nucl Med 35:391–398

    CAS  PubMed  Google Scholar 

  • Scheltens P, Rockwood K (2011) How golden is the gold standard of neuropathology in dementia? Alzheimers Dement 7:486–489

    PubMed  Google Scholar 

  • Schöll M, Almqvist O, Graff C et al (2011) Amyloid imaging in members of a family harbouring the Arctic mutation. Alzheimers Dement 7(Suppl 1):303

    Google Scholar 

  • Schulz-Schaeffer WJ (2010) The synaptic pathology of alpha-synuclein aggregation in dementia with Lewy bodies, Parkinson’s disease and Parkinson’s disease dementia. Acta Neuropathol 120:131–143

    CAS  PubMed Central  PubMed  Google Scholar 

  • Serdons K, Verduyckt T, Cleynhens J et al (2007) Synthesis and evaluation of a (99m)Tc-BAT-phenylbenzothiazole conjugate as a potential in vivo tracer for visualization of amyloid beta. Bioorg Med Chem Lett 17:6086–6090

    CAS  PubMed  Google Scholar 

  • Serdons K, Terwinghe C, Vermaelen P et al (2009a) Synthesis and evaluation of (18)F-Labeled 2-Phenylbenzothiazoles as positron emission tomography imaging agents for amyloid plaques in Alzheimer’s disease. J Med Chem 52:1428–1437

    Google Scholar 

  • Serdons K, Verduyckt T, Vanderghinste D et al (2009b) Synthesis of 18F-labelled 2-(4'-fluorophenyl)-1,3-benzothiazole and evaluation as amyloid imaging agent in comparison with [11C]PIB. Bioorg Med Chem Lett 19:602–605

    CAS  PubMed  Google Scholar 

  • Shaw LM, Korecka M, Clark CM et al (2007) Biomarkers of neurodegeneration for diagnosis and monitoring therapeutics. Nat Rev Drug Discov 6:295–303

    CAS  PubMed  Google Scholar 

  • Shih WJ, Markesbery WR, Clark DB et al (1987) Iodine-123 HIPDM brain imaging findings in subacute spongiform encephalopathy (Creutzfeldt-Jakob disease). J Nucl Med 28:1484–1487

    CAS  PubMed  Google Scholar 

  • Shoghi-Jadid K, Small GW, Agdeppa ED et al (2002) Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease. Am J Geriatr Psychiatry 10:24–35

    PubMed  Google Scholar 

  • Siderowf A, Xie SX, Hurtig H et al (2010) CSF amyloid beta 1–42 predicts cognitive decline in Parkinson disease. Neurology 75:1055–1061

    CAS  PubMed Central  PubMed  Google Scholar 

  • Silverman DH, Small GW, Chang CY et al (2001) Positron emission tomography in evaluation of dementia: regional brain metabolism and long-term outcome. JAMA 286:2120–2127

    CAS  PubMed  Google Scholar 

  • Silverman DH, Cummings JL, Small GW et al (2002) Added clinical benefit of incorporating 2-deoxy-2-[18F]fluoro-D-glucose with positron emission tomography into the clinical evaluation of patients with cognitive impairment. Mol Imaging Biol 4:283–293

    PubMed  Google Scholar 

  • Small GW, Mazziotta JC, Collins MT et al (1995) Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease. JAMA 273:942–947

    CAS  PubMed  Google Scholar 

  • Small GW, Agdeppa ED, Kepe V et al (2002) In vivo brain imaging of tangle burden in humans. J Mol Neurosci 19:323–327

    CAS  PubMed  Google Scholar 

  • Small GW, Kepe V, Ercoli LM et al (2006) PET of brain amyloid and tau in mild cognitive impairment. N Engl J Med 355:2652–2663

    CAS  PubMed  Google Scholar 

  • Small BJ, Gagnon E, Robinson B (2007) Early identification of cognitive deficits: preclinical Alzheimer’s disease and mild cognitive impairment. Geriatrics 62:19–23

    PubMed  Google Scholar 

  • Smith EE, Egorova S, Blacker D et al (2008) Magnetic resonance imaging white matter hyperintensities and brain volume in the prediction of mild cognitive impairment and dementia. Arch Neurol 65:94–100

    PubMed  Google Scholar 

  • Snowden J, Neary D, Mann D (2007) Frontotemporal lobar degeneration: clinical and pathological relationships. Acta Neuropathol 114:31–38

    PubMed  Google Scholar 

  • Sojkova J, Resnick SM (2011) In vivo human amyloid imaging. Curr Alzheimer Res 8:366–372

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sojkova J, Driscoll I, Iacono D et al (2011a) In vivo fibrillar beta-amyloid detected using [11C]PiB positron emission tomography and neuropathologic assessment in older adults. Arch Neurol 68:232–240

    PubMed Central  PubMed  Google Scholar 

  • Sojkova J, Zhou Y, An Y et al (2011b) Longitudinal patterns of beta-amyloid deposition in nondemented older adults. Arch Neurol 68:644–649

    PubMed Central  PubMed  Google Scholar 

  • Song PJ, Bernard S, Sarradin P et al (2008) IMPY, a potential beta-amyloid imaging probe for detection of prion deposits in scrapie-infected mice. Nucl Med Biol 35:197–201

    CAS  PubMed  Google Scholar 

  • Sperling R, Johnson K (2010) Pro: can biomarkers be gold standards in Alzheimer’s disease? Alzheimers Res Ther 2:17

    PubMed Central  PubMed  Google Scholar 

  • Sperling RA, Laviolette PS, O’Keefe K et al (2009) Amyloid deposition is associated with impaired default network function in older persons without dementia. Neuron 63:178–188

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sperling RA, Aisen PS, Beckett LA et al (2011a) Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7:280–292

    PubMed Central  PubMed  Google Scholar 

  • Sperling RA, Jack CR Jr, Aisen PS (2011b) Testing the right target and right drug at the right stage. Sci Transl Med 3:111cm133

    Google Scholar 

  • Sperling RA, Jack CR Jr, Black SE et al (2011c) Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: recommendations from the Alzheimer’s Association Research Roundtable Workgroup. Alzheimers Dement 7:367–385

    PubMed Central  PubMed  Google Scholar 

  • Sperling RA, Johnson KA, Doraiswamy PM et al (2012) Amyloid deposition detected with florbetapir F 18 ((18)F-AV-45) is related to lower episodic memory performance in clinically normal older individuals. Neurobiol Aging 34(3):822–831

    PubMed Central  PubMed  Google Scholar 

  • Stern Y (2002) What is cognitive reserve? Theory and research application of the reserve concept. J Int Neuropsychol Soc 8:448–460

    PubMed  Google Scholar 

  • Storandt M, Head D, Fagan AM et al (2012) Toward a multifactorial model of Alzheimer disease. Neurobiol Aging 33:2262–2271

    Google Scholar 

  • Strozyk D, Blennow K, White LR et al (2003) CSF Abeta 42 levels correlate with amyloid-neuropathology in a population-based autopsy study. Neurology 60:652–656

    CAS  PubMed  Google Scholar 

  • Sunderland T, Gur RE, Arnold SE (2005) The use of biomarkers in the elderly: current and future challenges. Biol Psychiatry 58:272–276

    CAS  PubMed  Google Scholar 

  • Sundgren-Andersson AK, Svensson SPS, Swahn BM et al (2009) AZD4694: fluorinated Positron Emission Tomography (PET) radioligand for detection of beta-amyloid deposits. Alzheimers Dement 5:P267–P268 [abstract]

    Google Scholar 

  • Suo Z, Wu M, Citron BA et al (2004) Abnormality of G-protein-coupled receptor kinases at prodromal and early stages of Alzheimer’s disease: an association with early beta-amyloid accumulation. J Neurosci 24:3444–3452

    CAS  PubMed  Google Scholar 

  • Sur C, Zeng Z, Hostetler E et al (2010) In vitro characterization of MK-3328: a novel fluorinated positron emission tomography tracer for beta-amyloid plaques. Alzheimers Dement 6:S40

    Google Scholar 

  • Taniguchi S, McDonagh AM, Pickering-Brown SM et al (2004) The neuropathology of frontotemporal lobar degeneration with respect to the cytological and biochemical characteristics of tau protein. Neuropathol Appl Neurobiol 30:1–18

    CAS  PubMed  Google Scholar 

  • Tenovuo O, Kemppainen N, Aalto S et al (2008) Posterior cortical atrophy: a rare form of dementia with in vivo evidence of amyloid-beta accumulation. J Alzheimers Dis 15:351–355

    CAS  PubMed  Google Scholar 

  • Thal DR, Del Tredici K, Braak H (2004) Neurodegeneration in normal brain aging and disease. Sci Aging Knowl Environ 2004:pe26

    Google Scholar 

  • Thal LJ, Kantarci K, Reiman EM et al (2006) The role of biomarkers in clinical trials for Alzheimer disease. Alzheimer Dis Assoc Disord 20:6–15

    PubMed Central  PubMed  Google Scholar 

  • Thompson PW, Ye L, Morgenstern JL et al (2009) Interaction of the amyloid imaging tracer FDDNP with hallmark Alzheimer’s disease pathologies. J Neurochem 109:623–630

    CAS  PubMed Central  PubMed  Google Scholar 

  • Thurfjell L, Lotjonen J, Lundqvist R et al (2012) Combination of biomarkers: PET [F]Flutemetamol imaging and structural MRI in dementia and mild cognitive impairment. Neurodegener Dis 10:246–249

    Google Scholar 

  • Tolboom N, van der Flier WM, Yaqub M et al (2009a) Relationship of cerebrospinal fluid markers to 11C-PiB and 18F-FDDNP binding. J Nucl Med 50:1464–1470

    CAS  PubMed  Google Scholar 

  • Tolboom N, Yaqub M, van der Flier WM et al (2009b) Detection of Alzheimer pathology in vivo using both 11C-PIB and 18F-FDDNP PET. J Nucl Med 50:191–197

    PubMed  Google Scholar 

  • Tomiyama T, Nagata T, Shimada H et al (2008) A new amyloid beta variant favoring oligomerization in Alzheimer’s-type dementia. Ann Neurol 63:377–387

    CAS  PubMed  Google Scholar 

  • Tosun D, Schuff N, Mathis CA et al (2011) Spatial patterns of brain amyloid-beta burden and atrophy rate associations in mild cognitive impairment. Brain 134:1077–1088

    PubMed Central  PubMed  Google Scholar 

  • Trojanowski JQ (2002) Emerging Alzheimer’s disease therapies: focusing on the future. Neurobiol Aging 23:985–990

    PubMed  Google Scholar 

  • Tucker AM, Stern Y (2011) Cognitive reserve in aging. Curr Alzheimer Res 8:354–360

    CAS  PubMed Central  PubMed  Google Scholar 

  • Vandenberghe R, Thurfjell L, Van Laere K et al (2010a) Comparison between cerebellum and pons as reference regions for quantification of the amyloid imaging agents [18F]flutemetamol and [11C]PIB. In: Proceedings of the human amyloid imaging Toronto, Canada, p. 42 [abstract]

    Google Scholar 

  • Vandenberghe R, Van Laere K, Ivanoiu A, et al (2010b) 18F-flutemetamol amyloid imaging in Alzheimer disease and mild cognitive impairment: a phase 2 trial. Ann Neurol 68:319–329

    Google Scholar 

  • Venneti S, Lopresti BJ, Wiley CA (2006) The peripheral benzodiazepine receptor (Translocator protein 18kDa) in microglia: from pathology to imaging. Prog Neurobiol 80:308–322

    CAS  PubMed Central  PubMed  Google Scholar 

  • Verhoeff NP, Wilson AA, Takeshita S et al (2004) In-vivo imaging of Alzheimer disease beta-amyloid with [11C]SB-13 PET. Am J Geriatr Psychiatry 12:584–595

    PubMed  Google Scholar 

  • Vernooij MW, van der Lugt A, Ikram MA et al (2008) Prevalence and risk factors of cerebral microbleeds: the Rotterdam Scan Study. Neurology 70:1208–1214

    CAS  PubMed  Google Scholar 

  • Villain N, Chetelat G, Grassiot B et al (2012) Regional dynamics of amyloid-beta deposition in healthy elderly, mild cognitive impairment and Alzheimer’s disease: a voxelwise PiB-PET longitudinal study. Brain 135:2126–2139

    PubMed  Google Scholar 

  • Villemagne VL, Rowe CC (2010) Amyloid ligands for dementia. PET Clin 5:33–53

    Google Scholar 

  • Villemagne VL, Rowe CC, Macfarlane S et al (2005) Imaginem oblivionis: the prospects of neuroimaging for early detection of Alzheimer’s disease. J Clin Neurosci 12:221–230

    PubMed  Google Scholar 

  • Villemagne VL, Cappai R, Barnham KJ et al (2006) The Aβ centric pathway of Alzheimer’s disease. In: Barrow CJ, Small BJ (eds) Abeta peptide and Alzheimer’s disease. Springer, London, pp 5–32

    Google Scholar 

  • Villemagne VL, Fodero-Tavoletti MT, Pike KE et al (2008a) The ART of loss: Aβ imaging in the evaluation of Alzheimer’s disease and other dementias. Mol Neurobiol 38:1–15

    CAS  PubMed  Google Scholar 

  • Villemagne VL, Pike KE, Darby D et al (2008b) Aβ deposits in older non-demented individuals with cognitive decline are indicative of preclinical Alzheimer’s disease. Neuropsychologia 46:1688–1697

    CAS  PubMed  Google Scholar 

  • Villemagne VL, Ataka S, Mizuno T et al (2009a) High striatal amyloid beta-peptide deposition across different autosomal Alzheimer disease mutation types. Arch Neurol 66:1537–1544

    PubMed  Google Scholar 

  • Villemagne VL, McLean CA, Reardon K et al (2009b) 11C-PiB PET studies in typical sporadic Creutzfeldt-Jakob disease. J Neurol Neurosurg Psychiatry 80:998–1001

    CAS  PubMed  Google Scholar 

  • Villemagne VL, Pike K, Pejoska S et al (2010) 11C-PiB PET ABri imaging in Worster-Drought syndrome (familial British dementia): a case report. J Alzheimers Dis 19:423–428

    CAS  PubMed  Google Scholar 

  • Villemagne VL, Ong K, Mulligan RS et al (2011a) Amyloid imaging with 18F-florbetaben in Alzheimer disease and other dementias. J Nucl Med 52:1210–1217

    PubMed  Google Scholar 

  • Villemagne VL, Pike KE, Chetelat G et al (2011b) Longitudinal assessment of Aβ and cognition in aging and Alzheimer disease. Ann Neurol 69:181–192

    CAS  PubMed Central  PubMed  Google Scholar 

  • Villemagne VL, Furumoto S, Fodero-Tavoletti MT et al (2012a) In vivo tau imaging in Alzheimer’s disease and other dementias. Alzheimers Dement 8:P9

    Google Scholar 

  • Villemagne VL, Klunk WE, Mathis CA et al (2012b) Abeta imaging: feasible, pertinent, and vital to progress in Alzheimer’s disease. Eur J Nucl Med Mol Imaging 39:209–219

    PubMed Central  PubMed  Google Scholar 

  • Villemagne VL, Mulligan RS, Pejoska S et al (2012c) Comparison of (11)C-PiB and (18)F-florbetaben for Aβ imaging in ageing and Alzheimer’s disease. Eur J Nucl Med Mol Imaging 39:983–989

    CAS  PubMed  Google Scholar 

  • Villemagne VL, Okamura N, Pejoska S et al (2012d) Differential diagnosis in Alzheimer’s disease and dementia with Lewy bodies via VMAT2 and amyloid imaging. Neurodegener Dis 10:161–165

    CAS  PubMed  Google Scholar 

  • Viswanathan A, Rocca WA, Tzourio C (2009) Vascular risk factors and dementia: how to move forward? Neurology 72:368–374

    PubMed Central  PubMed  Google Scholar 

  • Vlassenko AG, Mintun MA, Xiong C et al (2011) Amyloid-beta plaque growth in cognitively normal adults: longitudinal [11C] Pittsburgh Compound B data. Ann Neurol 70:857–861

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wahlund LO, Blennow K (2003) Cerebrospinal fluid biomarkers for disease stage and intensity in cognitively impaired patients. Neurosci Lett 339:99–102

    CAS  PubMed  Google Scholar 

  • Walker LC, Rosen RF, Levine H 3rd (2008) Diversity of Abeta deposits in the aged brain: a window on molecular heterogeneity? Rom J Morphol Embryol 49:5–11

    CAS  PubMed  Google Scholar 

  • Weller RO, Preston SD, Subash M et al (2009) Cerebral amyloid angiopathy in the aetiology and immunotherapy of Alzheimer disease. Alzheimers Res Ther 1:6

    PubMed Central  PubMed  Google Scholar 

  • Wermke M, Sorg C, Wohlschlager AM et al (2008) A new integrative model of cerebral activation, deactivation and default mode function in Alzheimer’s disease. Eur J Nucl Med Mol Imaging 35(Suppl 1):S12–S24

    PubMed  Google Scholar 

  • Wiley CA, Lopresti BJ, Venneti S et al (2009) Carbon 11-labeled Pittsburgh Compound B and carbon 11-labeled (R)-PK11195 positron emission tomographic imaging in Alzheimer disease. Arch Neurol 66:60–67

    PubMed Central  PubMed  Google Scholar 

  • Winblad B, Palmer K, Kivipelto M et al (2004) Mild cognitive impairment–beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med 256:240–246

    CAS  PubMed  Google Scholar 

  • Wolk DA, Price JC, Saxton JA et al (2009) Amyloid imaging in mild cognitive impairment subtypes. Ann Neurol 65:557–568

    PubMed Central  PubMed  Google Scholar 

  • Wolk DA, Grachev ID, Buckley C et al (2011) Association between in vivo fluorine 18-labeled flutemetamol amyloid positron emission tomography imaging and in vivo cerebral cortical histopathology. Arch Neurol 68:1398–1403

    PubMed  Google Scholar 

  • Wolk DA, Price JC, Madeira C et al (2012a) Amyloid imaging in dementias with atypical presentation. Alzheimers Dement 8:389–398

    Google Scholar 

  • Wolk DA, Zhang Z, Boudhar S et al (2012b) Amyloid imaging in Alzheimer’s disease: comparison of florbetapir and Pittsburgh Compound-B positron emission tomography. J Neurol Neurosurg Psychiatry 83:923–926

    PubMed  Google Scholar 

  • Wong DF, Rosenberg PB, Zhou Y et al (2010) In vivo imaging of amyloid deposition in Alzheimer disease using the radioligand 18F-AV-45 (florbetapir [corrected] F 18). J Nucl Med 51:913–920

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wong DF, Moghekar AR, Rigamonti D et al (2013) An In vivo evaluation of cerebral cortical amyloid with [(18)F]flutemetamol using positron emission tomography compared with parietal biopsy samples in living normal pressure hydrocephalus patients. Mol Imaging Biol 15(2):230–237

    PubMed Central  PubMed  Google Scholar 

  • Yates PA, Sirisriro R, Villemagne VL et al (2011) Cerebral microhemorrhage and brain {beta}-amyloid in aging and Alzheimer disease. Neurology 77:48–54

    CAS  PubMed  Google Scholar 

  • Ye L, Morgenstern JL, Gee AD et al (2005) Delineation of positron emission tomography imaging agent binding sites on beta-amyloid peptide fibrils. J Biol Chem 280:23599–23604

    CAS  PubMed  Google Scholar 

  • Ye L, Velasco A, Fraser G et al (2008) In vitro high affinity alpha-synuclein binding sites for the amyloid imaging agent PIB are not matched by binding to Lewy bodies in postmortem human brain. J Neurochem 105:1428–1437

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yee S, Mathis C, Klunk W et al (2007) Optimal time window for standardized uptake ratio as a simplified measure of PIB retention. J Nucl Med 48:404P

    Google Scholar 

  • Yokokura M, Mori N, Yagi S et al (2011) In vivo changes in microglial activation and amyloid deposits in brain regions with hypometabolism in Alzheimer’s disease. Eur J Nucl Med Mol Imaging 38:343–351

    CAS  PubMed  Google Scholar 

  • Zhang W, Oya S, Kung MP et al (2005a) F-18 polyethyleneglycol stilbenes as PET imaging agents targeting Abeta aggregates in the brain. Nucl Med Biol 32:799–809

    CAS  PubMed  Google Scholar 

  • Zhang W, Oya S, Kung MP et al (2005b) F-18 stilbenes as PET imaging agents for detecting beta-amyloid plaques in the brain. J Med Chem 48:5980–5988

    CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgements

We thank Prof. Michael Woodward, Dr. John Merory, Dr. Peter Drysdale, Dr. Gordon Chan, Dr. Kenneth Young, Dr. Sylvia Gong, Dr. Greg Savage, Dr. Paul Maruff, Dr. David Darby, Ms. Fiona Lamb, Mr. Sean Thronton, Ms. Mary Kate Danaher, Ms. Joanne Robertson and the Brain Research Institute for their assistance with this study.

This work was supported in part by grant 1011689 of the National Health and Medical Research Council of Australia, the Science and Industry Endowment Fund, and the Austin Hospital Medical Research Foundation.

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Authors and Affiliations

  1. Division of Nuclear Medicine and Centre for PET, Austin Health, 145 Studley Rd, Heidelberg, VIC, 3084, Australia

    Victor L. Villemagne MD, Paul Yates MD & Christopher C. Rowe MD

  2. Department of Medicine, University of Melbourne, Austin Health, Heidelberg, VIC, 3084, Australia

    Victor L. Villemagne MD

  3. The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, 3010, Australia

    Victor L. Villemagne MD

  4. The Florey Institute of Neuroscience and Mental Health, 30 Royal Parade, Parkville, Melbourne, VIC, 3052, Australia

    Michelle Fodero-Tavoletti PhD & Colin L. Masters MD

  5. Department of Nuclear Medicine and Centre for PET, Austin Health, 145 Studley Road, Heidelberg, Melbourne, VIC, 3084, Australia

    Michelle Fodero-Tavoletti PhD & Colin L. Masters MD

  6. Department of Medicine, University of Melbourne, Austin Health, Heidelberg, VIC, 3084, Australia

    Christopher C. Rowe MD

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  1. Victor L. Villemagne MD
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Correspondence to Victor L. Villemagne MD .

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Editors and Affiliations

  1. Dept. of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

    Rudi A.J.O. Dierckx

  2. Faculty of Electrical Engineering and Information Technology, University of Applied Sciences Offenburg, Offenburg, Germany

    Andreas Otte

  3. Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands

    Erik F.J. de Vries

  4. Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands

    Aren van Waarde

  5. Neurology, University Medical Center Groningen, Groningen, The Netherlands

    Klaus L. Leenders

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Villemagne, V.L., Fodero-Tavoletti, M., Yates, P., Masters, C.L., Rowe, C.C. (2014). Aβ Imaging in Aging, Alzheimer’s Disease and Other Neurodegenerative Conditions. In: Dierckx, R., Otte, A., de Vries, E., van Waarde, A., Leenders, K. (eds) PET and SPECT in Neurology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-54307-4_10

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