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Amyloid-β PET Imaging in Aging and Dementia

  • Nelleke TolboomEmail author
  • Rik Ossenkoppele
  • Bart N. van Berckel
Chapter
Part of the Clinicians’ Guides to Radionuclide Hybrid Imaging book series (CGRHI)

Abstract

Amyloid-β imaging with positron emission tomography (PET) has been around since the early 2000s. It has transformed neuroimaging in Alzheimer’s disease (AD) by facilitating in vivo detection (and quantification) of amyloid-β plaques, one of the core pathological features of AD [1]. Initially, it was primarily used for research purposes and only infrequently in clinical practice. Now, more than a decade after the initial publications, it has become a standard diagnostic aid in specialised memory clinics.

References

  1. 1.
    Hardy J, Allsop D. Amyloid deposition as the central event in the aetiology of Alzheimer’s disease. Trends Pharmacol Sci. 1991;12(10):383–8.PubMedGoogle Scholar
  2. 2.
    Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt DP, et al. Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol. 2004;55(3):306–19.Google Scholar
  3. 3.
    Ikonomovic MD, Klunk WE, Abrahamson EE, Mathis CA, Price JC, Tsopelas ND, et al. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease. Brain. 2008;131(Pt 6):1630–45.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Bergeron D, Ossenkoppele R Jr, Laforce R. Evidence-based interpretation of amyloid-beta PET results: a clinician’s tool. Alzheimer Dis Assoc Disord. 2018;32(1):28–34.PubMedGoogle Scholar
  5. 5.
    Scholl M, Wall A, Thordardottir S, Ferreira D, Bogdanovic N, Langstrom B, et al. Low PiB PET retention in presence of pathologic CSF biomarkers in Arctic APP mutation carriers. Neurology. 2012;79(3):229–36.PubMedGoogle Scholar
  6. 6.
    Tomiyama T, Nagata T, Shimada H, Teraoka R, Fukushima A, Kanemitsu H, et al. A new amyloid beta variant favoring oligomerization in Alzheimer’s-type dementia. Ann Neurol. 2008;63(3):377–87.PubMedGoogle Scholar
  7. 7.
    Rowe CC, Ellis KA, Rimajova M, Bourgeat P, Pike KE, Jones G, et al. Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Neurobiol Aging. 2010;31(8):1275–83.PubMedGoogle Scholar
  8. 8.
    Clark CM, Schneider JA, Bedell BJ, Beach TG, Bilker WB, Mintun MA, et al. Use of florbetapir-PET for imaging beta-amyloid pathology. JAMA. 2011;305(3):275–83.PubMedGoogle Scholar
  9. 9.
    Vandenberghe R, Van Laere K, Ivanoiu A, Salmon E, Bastin C, Triau E, et al. 18F-flutemetamol amyloid imaging in Alzheimer disease and mild cognitive impairment: a phase 2 trial. Ann Neurol. 2010;68(3):319–29.PubMedGoogle Scholar
  10. 10.
    Barthel H, Gertz HJ, Dresel S, Peters O, Bartenstein P, Buerger K, et al. Cerebral amyloid-beta PET with florbetaben (18F) in patients with Alzheimer’s disease and healthy controls: a multicentre phase 2 diagnostic study. Lancet Neurol. 2011;10(5):424–35.PubMedGoogle Scholar
  11. 11.
    Landau SM, Breault C, Joshi AD, Pontecorvo M, Mathis CA, Jagust WJ, et al. Amyloid-beta imaging with Pittsburgh compound B and florbetapir: comparing radiotracers and quantification methods. J Nucl Med. 2013;54(1):70–7.PubMedGoogle Scholar
  12. 12.
    Wolk DA, Zhang Z, Boudhar S, Clark CM, Pontecorvo MJ, Arnold SE. Amyloid imaging in Alzheimer’s disease: comparison of florbetapir and Pittsburgh compound-B positron emission tomography. J Neurol Neurosurg Psychiatry. 2012;83(9):923–6.PubMedPubMedCentralGoogle Scholar
  13. 13.
    Villemagne VL, Mulligan RS, Pejoska S, Ong K, Jones G, O’Keefe G, et al. Comparison of 11C-PiB and 18F-florbetaben for Abeta imaging in ageing and Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2012;39(6):983–9.PubMedGoogle Scholar
  14. 14.
    Johnson KA, Minoshima S, Bohnen NI, Donohoe KJ, Foster NL, Herscovitch P, et al. Appropriate use criteria for amyloid PET: a report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer’s Association. Alzheimers Dement. 2013;9(1):16.Google Scholar
  15. 15.
    Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004;256(3):183–94.PubMedGoogle Scholar
  16. 16.
    Jansen WJ, Ossenkoppele R, Knol DL, Tijms BM, Scheltens P, Verhey FR, et al. Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis. JAMA. 2015;313(19):1924–38.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Villemagne VL, Pike KE, Chetelat G, Ellis KA, Mulligan RS, Bourgeat P, et al. Longitudinal assessment of Abeta and cognition in aging and Alzheimer disease. Ann Neurol. 2011;69(1):181–92.PubMedPubMedCentralGoogle Scholar
  18. 18.
    McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR, Kawas CH, et al. 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. 2011;7(3):263–9.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Rabinovici GD, Miller BL. Frontotemporal lobar degeneration: epidemiology, pathophysiology, diagnosis and management. CNS Drugs. 2010;24(5):375–98.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Alladi S, Xuereb J, Bak T, Nestor P, Knibb J, Patterson K, et al. Focal cortical presentations of Alzheimer’s disease. Brain. 2007;130(Pt 10):2636–45.PubMedGoogle Scholar
  21. 21.
    Ossenkoppele R, Jansen WJ, Rabinovici GD, Knol DL, van der Flier WM, van Berckel BN, et al. Prevalence of amyloid PET positivity in dementia syndromes: a meta-analysis. JAMA. 2015;313(19):1939–49.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Mackenzie IR, Neumann M, Bigio EH, Cairns NJ, Alafuzoff I, Kril J, et al. Nomenclature and nosology for neuropathologic subtypes of frontotemporal lobar degeneration: an update. Acta Neuropathol. 2010;119(1):1–4.PubMedGoogle Scholar
  23. 23.
    Mintun MA, Larossa GN, Sheline YI, Dence CS, Lee SY, Mach RH, et al. [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurology. 2006;67(3):446–52.PubMedGoogle Scholar
  24. 24.
    Morris JC, Roe CM, Xiong C, Fagan AM, Goate AM, Holtzman DM, et al. APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging. Ann Neurol. 2010;67(1):122–31.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Rabinovici GD, Furst AJ, O’Neil JP, Racine CA, Mormino EC, Baker SL, et al. 11C-PIB PET imaging in Alzheimer disease and frontotemporal lobar degeneration. Neurology. 2007;68(15):1205–12.PubMedGoogle Scholar
  26. 26.
    Rowe CC, Ng S, Ackermann U, Gong SJ, Pike K, Savage G, et al. Imaging beta-amyloid burden in aging and dementia. Neurology. 2007;68(20):1718–25.PubMedGoogle Scholar
  27. 27.
    Gomperts SN, Rentz DM, Moran E, Becker JA, Locascio JJ, Klunk WE, et al. Imaging amyloid deposition in Lewy body diseases. Neurology. 2008;71(12):903–10.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Ballard C, Ziabreva I, Perry R, Larsen JP, O’Brien J, McKeith I, et al. Differences in neuropathologic characteristics across the Lewy body dementia spectrum. Neurology. 2006;67(11):1931–4.PubMedGoogle Scholar
  29. 29.
    Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, et al. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med. 2012;367(9):795–804.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Price JL, McKeel DW, Buckles VD, Roe CM, Xiong C, Grundman M, et al. Neuropathology of nondemented aging: presumptive evidence for preclinical Alzheimer disease. Neurobiol Aging. 2009;30(7):1026–36.PubMedPubMedCentralGoogle Scholar
  31. 31.
    Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, et al. Amyloid beta deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. Lancet Neurol. 2013;12(4):357–67.PubMedGoogle Scholar
  32. 32.
    Villain N, Chetelat G, Grassiot B, Bourgeat P, Jones G, Ellis KA, et al. Regional dynamics of amyloid-beta deposition in healthy elderly, mild cognitive impairment and Alzheimer’s disease: a voxelwise PiB-PET longitudinal study. Brain. 2012;135.(Pt 7:2126–39.PubMedGoogle Scholar
  33. 33.
    Thal DR, Rub U, Orantes M, Braak H. Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology. 2002;58(12):1791–800.Google Scholar
  34. 34.
    Frings L, Hellwig S, Spehl TS, Bormann T, Buchert R, Vach W, et al. Asymmetries of amyloid-beta burden and neuronal dysfunction are positively correlated in Alzheimer’s disease. Brain. 2015;138(Pt 10):3089–99.PubMedGoogle Scholar
  35. 35.
    Ossenkoppele R, Zwan MD, Tolboom N, van Assema DM, Adriaanse SF, Kloet RW, et al. Amyloid burden and metabolic function in early-onset Alzheimer’s disease: parietal lobe involvement. Brain. 2012;135(Pt 7):2115–25.PubMedGoogle Scholar
  36. 36.
    Martersteck A, Murphy C, Rademaker A, Wieneke C, Weintraub S, Chen K, et al. Is in vivo amyloid distribution asymmetric in primary progressive aphasia? Ann Neurol. 2016;79(3):496–501.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Klunk WE, Price JC, Mathis CA, Tsopelas ND, Lopresti BJ, Ziolko SK, et al. Amyloid deposition begins in the striatum of presenilin-1 mutation carriers from two unrelated pedigrees. J Neurosci. 2007;27(23):6174–84.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Zwan MD, Bouwman FH, Konijnenberg E, van der Flier WM, Lammertsma AA, Verhey FR, et al. Diagnostic impact of [(18)F]flutemetamol PET in early-onset dementia. Alzheimers Res Ther. 2017;9(1):4.Google Scholar
  39. 39.
    Ossenkoppele R, Prins ND, Pijnenburg YA, Lemstra AW, van der Flier WM, Adriaanse SF, et al. Impact of molecular imaging on the diagnostic process in a memory clinic. Alzheimers Dement. 2013;9(4):414–21.PubMedGoogle Scholar
  40. 40.
    Grundman M, Johnson KA, Lu M, Siderowf A, Dell’Agnello G, Arora AK, et al. Effect of amyloid imaging on the diagnosis and management of patients with cognitive decline: impact of appropriate use criteria. Dement Geriatr Cogn Disord. 2016;41(1–2):80–92.PubMedGoogle Scholar
  41. 41.
    Barthel H, Sabri O. Clinical use and utility of amyloid imaging. J Nucl Med. 2017;58(11):1711–7.PubMedGoogle Scholar
  42. 42.
    Ben Bouallegue F, Mariano-Goulart D, Payoux P, Alzheimer’s Disease Neuroimaging Initiative (ADNI). Comparison of CSF markers and semi-quantitative amyloid PET in Alzheimer’s disease diagnosis and in cognitive impairment prognosis using the ADNI-2 database. Alzheimers Res Ther. 2017;9(1):32.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Mattsson N, Insel PS, Donohue M, Landau S, Jagust WJ, Shaw LM, et al. Independent information from cerebrospinal fluid amyloid-beta and florbetapir imaging in Alzheimer’s disease. Brain. 2015;138(Pt 3):772–83.PubMedGoogle Scholar
  44. 44.
    Hornberger J, Michalopoulos S, Dai M, Andrade P, Dilla T, Happich M. Cost-effectiveness of florbetapir-PET in Alzheimer’s disease: a Spanish Societal perspective. J Ment Health Policy Econ. 2015;18(2):63–73.PubMedGoogle Scholar
  45. 45.
    Hornberger J, Bae J, Watson I, Johnston J, Happich M. Clinical and cost implications of amyloid beta detection with amyloid beta positron emission tomography imaging in early Alzheimer’s disease - the case of florbetapir. Curr Med Res Opin. 2017;33(4):675–85.PubMedGoogle Scholar
  46. 46.
    Knopman DS, Parisi JE, Salviati A, Floriach-Robert M, Boeve BF, Ivnik RJ, et al. Neuropathology of cognitively normal elderly. J Neuropathol Exp Neurol. 2003;62(11):1087–95.PubMedGoogle Scholar
  47. 47.
    Reiman EM, Chen K, Liu X, Bandy D, Yu M, Lee W, et al. Fibrillar amyloid-beta burden in cognitively normal people at 3 levels of genetic risk for Alzheimer’s disease. Proc Natl Acad Sci U S A. 2009;106(16):6820–5.PubMedPubMedCentralGoogle Scholar
  48. 48.
    Jack CR Jr, Wiste HJ, Weigand SD, Therneau TM, Lowe VJ, Knopman DS, et al. Defining imaging biomarker cut points for brain aging and Alzheimer’s disease. Alzheimers Dement. 2017;13(3):205–16.PubMedGoogle Scholar
  49. 49.
    Klunk WE, Koeppe RA, Price JC, Benzinger TL, Devous MD Sr, Jagust WJ, et al. The Centiloid Project: standardizing quantitative amyloid plaque estimation by PET. Alzheimers Dement. 2015;11(1):4.Google Scholar
  50. 50.
    McNamee RL, Yee SH, Price JC, Klunk WE, Rosario B, Weissfeld L, et al. Consideration of optimal time window for Pittsburgh compound B PET summed uptake measurements. J Nucl Med. 2009;50(3):348–55.PubMedPubMedCentralGoogle Scholar
  51. 51.
    van Berckel BN, Ossenkoppele R, Tolboom N, Yaqub M, Foster-Dingley JC, Windhorst AD, et al. Longitudinal amyloid imaging using 11C-PiB: methodologic considerations. J Nucl Med. 2013;54(9):1570–6.PubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Nelleke Tolboom
    • 1
    Email author
  • Rik Ossenkoppele
    • 2
    • 3
  • Bart N. van Berckel
    • 4
  1. 1.Imaging Division, Department of RadiologyUniversity Medical Center UtrechtUtrechtThe Netherlands
  2. 2.Alzheimer CenterAmsterdam University Medical CenterAmsterdamThe Netherlands
  3. 3.Clinical Memory Research UnitLund UniversityLundSweden
  4. 4.Department of Radiology and Nuclear MedicineAmsterdam University Medical CenterAmsterdamThe Netherlands

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