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In Vivo Volumetry of the Cholinergic Basal Forebrain

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Biomarkers for Preclinical Alzheimer’s Disease

Part of the book series: Neuromethods ((NM,volume 137))

Abstract

Degeneration of cortically projecting acetylcholine-containing neuronal populations within the basal forebrain cholinergic system (BFCS) is a central pathogenetic aspect of Alzheimer’s disease (AD) and forms the rationale for the use of cholinomimetics as antidementive treatment. The role of the cholinergic deficit in AD pathophysiology has mainly been studied in experimental animal models and in neuropathologic examinations of human autopsy data of advanced disease stages. Interactions between cholinergic deficits and accumulation of cortical amyloid pathology point to a relevant role of BFCS degeneration for the preclinical stage of AD. The advent of novel computational morphometry techniques for the automated analysis of high-resolution MRI data allows studying AD-related atrophy in the living human brain with ever-increasing temporal and regional detail. Combining these morphometry techniques with recently developed stereotactic mappings of the BFCS provides a method for automated MRI-based volumetry that can sensitively assess degenerative changes of the BFCS in vivo. Here, we outline the general methodological approach for MRI-based BFCS volumetry and describe the specifics of different image processing choices and analysis strategies. We further discuss possibilities and limitations of this method for studying BFCS degeneration in the course of AD, with a special emphasis on using MRI-based BFCS volumetry as an imaging biomarker for defining the preclinical disease stage.

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References

  1. Whitehouse PJ, Price DL, Struble RG et al (1982) Alzheimer's disease and senile dementia: loss of neurons in the basal forebrain. Science 215(4537):1237–1239

    Article  CAS  PubMed  Google Scholar 

  2. McGeer PL, McGeer EG, Suzuki J et al (1984) Aging, Alzheimer's disease, and the cholinergic system of the basal forebrain. Neurology 34(6):741–745

    Article  CAS  PubMed  Google Scholar 

  3. Vogels OJ, Broere CA, ter Laak HJ et al (1990) Cell loss and shrinkage in the nucleus basalis Meynert complex in Alzheimer's disease. Neurobiol Aging 11(1):3–13

    Article  CAS  PubMed  Google Scholar 

  4. Perry EK, Blessed G, Tomlinson BE et al (1981) Neurochemical activities in human temporal lobe related to aging and Alzheimer-type changes. Neurobiol Aging 2(4):251–256

    Article  CAS  PubMed  Google Scholar 

  5. Bartus RT, Dean RL 3rd, Beer B et al (1982) The cholinergic hypothesis of geriatric memory dysfunction. Science 217(4558):408–414

    Article  CAS  PubMed  Google Scholar 

  6. Birks J (2006) Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database Syst Rev 1:CD005593. https://doi.org/10.1002/14651858.cd005593

    Google Scholar 

  7. Perry EK, Tomlinson BE, Blessed G et al (1978) Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J 2(6150):1457–1459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ikonomovic MD, Klunk WE, Abrahamson EE et al (2011) Precuneus amyloid burden is associated with reduced cholinergic activity in Alzheimer disease. Neurology 77(1):39–47. https://doi.org/10.1212/WNL.0b013e3182231419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Beach TG, McGeer EG (1992) Senile plaques, amyloid beta-protein, and acetylcholinesterase fibres: laminar distributions in Alzheimer's disease striate cortex. Acta Neuropathol 83(3):292–299

    Article  CAS  PubMed  Google Scholar 

  10. Arendt T, Bigl V, Tennstedt A et al (1985) Neuronal loss in different parts of the nucleus basalis is related to neuritic plaque formation in cortical target areas in Alzheimer's disease. Neuroscience 14(1):1–14

    Article  CAS  PubMed  Google Scholar 

  11. Beach TG, Honer WG, Hughes LH (1997) Cholinergic fibre loss associated with diffuse plaques in the non-demented elderly: the preclinical stage of Alzheimer's disease? Acta Neuropathol 93(2):146–153

    Article  CAS  PubMed  Google Scholar 

  12. Potter PE, Rauschkolb PK, Pandya Y et al (2011) Pre- and post-synaptic cortical cholinergic deficits are proportional to amyloid plaque presence and density at preclinical stages of Alzheimer's disease. Acta Neuropathol 122(1):49–60. https://doi.org/10.1007/s00401-011-0831-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Beach TG, Kuo YM, Spiegel K et al (2000) The cholinergic deficit coincides with Abeta deposition at the earliest histopathologic stages of Alzheimer disease. J Neuropathol Exp Neurol 59(4):308–313

    Article  CAS  PubMed  Google Scholar 

  14. Young AL, Oxtoby NP, Daga P et al (2014) A data-driven model of biomarker changes in sporadic Alzheimer's disease. Brain 137(Pt 9):2564–2577. https://doi.org/10.1093/brain/awu176

    Article  PubMed  PubMed Central  Google Scholar 

  15. Jack CR Jr, Knopman DS, Jagust WJ et al (2013) Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol 12(2):207–216. https://doi.org/10.1016/s1474-4422(12)70291-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Huckman MS (1995) Where's the chicken? AJNR Am J Neuroradiol 16(10):2008–2009

    CAS  PubMed  Google Scholar 

  17. Hanyu H, Asano T, Sakurai H et al (2002) MR analysis of the substantia innominata in normal aging, Alzheimer disease, and other types of dementia. AJNR Am J Neuroradiol 23(1):27–32

    PubMed  Google Scholar 

  18. Zaborszky L, Hoemke L, Mohlberg H et al (2008) Stereotaxic probabilistic maps of the magnocellular cell groups in human basal forebrain. NeuroImage 42(3):1127–1141. https://doi.org/10.1016/j.neuroimage.2008.05.055

    Article  PubMed  PubMed Central  Google Scholar 

  19. Halliday GM, Cullen K, Cairns MJ (1993) Quantitation and three-dimensional reconstruction of Ch4 nucleus in the human basal forebrain. Synapse 15(1):1–16. https://doi.org/10.1002/syn.890150102

    Article  CAS  PubMed  Google Scholar 

  20. Teipel SJ, Flatz W, Ackl N et al (2014) Brain atrophy in primary progressive aphasia involves the cholinergic basal forebrain and Ayala's nucleus. Psychiatry Res 221(3):187–194. https://doi.org/10.1016/j.pscychresns.2013.10.003

    Article  PubMed  Google Scholar 

  21. Teipel SJ, Flatz WH, Heinsen H et al (2005) Measurement of basal forebrain atrophy in Alzheimer's disease using MRI. Brain 128(Pt 11):2626–2644. https://doi.org/10.1093/brain/awh589

    Article  PubMed  Google Scholar 

  22. Mesulam MM, Mufson EJ, Levey AI et al (1983) Cholinergic innervation of cortex by the basal forebrain: cytochemistry and cortical connections of the septal area, diagonal band nuclei, nucleus basalis (substantia innominata), and hypothalamus in the rhesus monkey. J Comp Neurol 214(2):170–197. https://doi.org/10.1002/cne.902140206

    Article  CAS  PubMed  Google Scholar 

  23. Zaborszky L, Csordas A, Mosca K et al (2013) Neurons in the basal forebrain project to the cortex in a complex topographic organization that reflects Corticocortical connectivity patterns: an experimental study based on retrograde tracing and 3D reconstruction. Cereb Cortex. https://doi.org/10.1093/cercor/bht210

  24. Muir JL (1997) Acetylcholine, aging, and Alzheimer’s disease. Pharmacol Biochem Behav 56(4):687–696

    Article  CAS  PubMed  Google Scholar 

  25. Pappas BA, Bayley PJ, Bui BK et al (2000) Choline acetyltransferase activity and cognitive domain scores of Alzheimer's patients. Neurobiol Aging 21(1):11–17

    Article  CAS  PubMed  Google Scholar 

  26. George S, Mufson EJ, Leurgans S et al (2011) MRI-based volumetric measurement of the substantia innominata in amnestic MCI and mild AD. Neurobiol Aging 32(10):1756–1764. https://doi.org/10.1016/j.neurobiolaging.2009.11.006

    Article  CAS  PubMed  Google Scholar 

  27. Hanyu H, Tanaka Y, Shimizu S et al (2005) Differences in MR features of the substantia innominata between dementia with Lewy bodies and Alzheimer's disease. J Neurol 252(4):482–484. https://doi.org/10.1007/s00415-005-0611-8

    Article  PubMed  Google Scholar 

  28. Gao FQ, Pettersen JA, Bocti C et al (2013) Is encroachment of the carotid termination into the substantia innominata associated with its atrophy and cognition in Alzheimer's disease? Neurobiol Aging 34(7):1807–1814. https://doi.org/10.1016/j.neurobiolaging.2013.01.009

    Article  PubMed  Google Scholar 

  29. Muth K, Schonmeyer R, Matura S et al (2010) Mild cognitive impairment in the elderly is associated with volume loss of the cholinergic basal forebrain region. Biol Psychiatry 67(6):588–591. https://doi.org/10.1016/j.biopsych.2009.02.026

    Article  CAS  PubMed  Google Scholar 

  30. Moon WJ, Kim HJ, Roh HG et al (2008) Atrophy measurement of the anterior commissure and substantia innominata with 3T high-resolution MR imaging: does the measurement differ for patients with frontotemporal lobar degeneration and Alzheimer disease and for healthy subjects? AJNR Am J Neuroradiol 29(7):1308–1313. https://doi.org/10.3174/ajnr.A1103

    Article  PubMed  Google Scholar 

  31. Teipel SJ, Meindl T, Grinberg L et al (2011) The cholinergic system in mild cognitive impairment and Alzheimer's disease: an in vivo MRI and DTI study. Hum Brain Mapp 32(9):1349–1362. https://doi.org/10.1002/hbm.21111

    Article  PubMed  Google Scholar 

  32. Grothe M, Zaborszky L, Atienza M et al (2010) Reduction of basal forebrain cholinergic system parallels cognitive impairment in patients at high risk of developing Alzheimer's disease. Cereb Cortex 20(7):1685–1695. https://doi.org/10.1093/cercor/bhp232

    Article  PubMed  Google Scholar 

  33. Grothe M, Heinsen H, Teipel SJ (2012) Atrophy of the cholinergic basal forebrain over the adult age range and in early stages of Alzheimer’s disease. Biol Psychiatry 71(9):805–813. https://doi.org/10.1016/j.biopsych.2011.06.019

    Article  CAS  PubMed  Google Scholar 

  34. Kilimann I, Grothe M, Heinsen H et al (2014) Subregional basal forebrain atrophy in Alzheimer's disease: a multicenter study. J Alzheimers Dis 40(3):687–700. https://doi.org/10.3233/jad-132345

    PubMed  PubMed Central  Google Scholar 

  35. Teipel S, Heinsen H, Amaro E Jr et al (2014) Cholinergic basal forebrain atrophy predicts amyloid burden in Alzheimer's disease. Neurobiol Aging 35(3):482–491. https://doi.org/10.1016/j.neurobiolaging.2013.09.029

    Article  CAS  PubMed  Google Scholar 

  36. Grothe MJ, Ewers M, Krause B et al (2014) Basal forebrain atrophy and cortical amyloid deposition in nondemented elderly subjects. Alzheimers Dement 10(5 Suppl):S344–S353. https://doi.org/10.1016/j.jalz.2013.09.011

    Article  PubMed  PubMed Central  Google Scholar 

  37. Kerbler GM, Fripp J, Rowe CC et al (2015) Basal forebrain atrophy correlates with amyloid beta burden in Alzheimer's disease. Neuroimage Clin 7:105–113. https://doi.org/10.1016/j.nicl.2014.11.015

    Article  PubMed  Google Scholar 

  38. Schmitz TW, Nathan Spreng R (2016) Basal forebrain degeneration precedes and predicts the cortical spread of Alzheimer's pathology. Nat Commun 7:13249. https://doi.org/10.1038/ncomms13249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Grothe M, Heinsen H, Teipel S (2013) Longitudinal measures of cholinergic forebrain atrophy in the transition from healthy aging to Alzheimer's disease. Neurobiol Aging 34(4):1210–1220. https://doi.org/10.1016/j.neurobiolaging.2012.10.018

    Article  CAS  PubMed  Google Scholar 

  40. Grothe MJ, Heinsen H, Amaro E Jr et al (2016) Cognitive correlates of basal forebrain atrophy and associated cortical Hypometabolism in mild cognitive impairment. Cereb Cortex 26(6):2411–2426. https://doi.org/10.1093/cercor/bhv062

    Article  PubMed  Google Scholar 

  41. Ray NJ, Metzler-Baddeley C, Khondoker MR et al (2015) Cholinergic basal forebrain structure influences the reconfiguration of white matter connections to support residual memory in mild cognitive impairment. J Neurosci 35(2):739–747. https://doi.org/10.1523/jneurosci.3617-14.2015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Cantero JL, Zaborszky L, Atienza M (2016) Volume loss of the nucleus Basalis of Meynert is associated with atrophy of innervated regions in mild cognitive impairment. Cereb Cortex. https://doi.org/10.1093/cercor/bhw195

  43. Grothe MJ, Scheef L, Bauml J et al (2016) Reduced cholinergic basal forebrain integrity links neonatal complications and adult cognitive deficits after premature birth. Biol Psychiatry. https://doi.org/10.1016/j.biopsych.2016.12.008

  44. Kilimann I, Hausner L, Fellgiebel A et al (2017) Parallel atrophy of cortex and basal forebrain cholinergic system in mild cognitive impairment. Cereb Cortex 27(3):1841–1848. https://doi.org/10.1093/cercor/bhw019

    PubMed  Google Scholar 

  45. Grinberg LT, Ferretti RE, Farfel JM et al (2007) Brain bank of the Brazilian aging brain study group - a milestone reached and more than 1,600 collected brains. Cell Tissue Bank 8(2):151–162. https://doi.org/10.1007/s10561-006-9022-z

    Article  PubMed  Google Scholar 

  46. Grinberg LT, Amaro E Jr, Teipel S et al (2008) Assessment of factors that confound MRI and neuropathological correlation of human postmortem brain tissue. Cell Tissue Bank 9(3):195–203. https://doi.org/10.1007/s10561-008-9080-5

    Article  PubMed  Google Scholar 

  47. Grinberg LT, Amaro Junior E, da Silva AV et al (2009) Improved detection of incipient vascular changes by a biotechnological platform combining post mortem MRI in situ with neuropathology. J Neurol Sci 283(1–2):2–8. https://doi.org/10.1016/j.jns.2009.02.327

    Article  PubMed  Google Scholar 

  48. Mesulam MM, Mufson EJ, Wainer BH et al (1983) Central cholinergic pathways in the rat: an overview based on an alternative nomenclature (Ch1-Ch6). Neuroscience 10(4):1185–1201

    Article  CAS  PubMed  Google Scholar 

  49. Reil JC (1809) Untersuchungen über den Bau des grossen Gehirns im Mensch. Arch Physiol (Halle) 9:136–146

    Google Scholar 

  50. Alheid GF, Heimer L (1988) New perspectives in basal forebrain organization of special relevance for neuropsychiatric disorders: the striatopallidal, amygdaloid, and corticopetal components of substantia innominata. Neuroscience 27:1–39

    Article  CAS  PubMed  Google Scholar 

  51. Heimer L, De Olmos J, Alheid GF et al (1991) “perestroika” in the basal forebrain: opening the border between neurology and psychiatry. Prog Brain Res 87:109–165

    Article  CAS  PubMed  Google Scholar 

  52. Lauer M, Heinsen H (1996) Cytoarchitectonics of the human nucleus accumbens. Journal of. Brain Res 37:243–254

    CAS  Google Scholar 

  53. Grinberg LT, Heinsen H (2007) Computer-assisted 3D reconstruction of the human basal forebrain. Dementia & Neuropsychologia 2:140–146

    Article  Google Scholar 

  54. Heinsen H, Hampel H, Teipel SJ (2006) Nucleus subputaminalis: neglected part of the basal nucleus of Meynert - response to Boban et al.: computer-assisted 3D reconstruction of the nucleus basalis complex, including the nucleus subputaminalis (Ayala's nucleus). Brain 129(4):U1–U4

    Article  Google Scholar 

  55. Ayala G (1915) A hitherto undifferentiated nucleus in the basal forebrain (nucleus subputaminalis). Brain 37:433–438

    Article  Google Scholar 

  56. Simic G, Mrzljak L, Fucic A et al (1999) Nucleus subputaminalis (Ayala): the still disregarded magnocellular component of the basal forebrain may be human specific and connected with the cortical speech area. Neuroscience 89(1):73–89

    Article  CAS  PubMed  Google Scholar 

  57. Ashburner J (2007) A fast diffeomorphic image registration algorithm. NeuroImage 38(1):95–113. https://doi.org/10.1016/j.neuroimage.2007.07.007

    Article  PubMed  Google Scholar 

  58. Klein A, Andersson J, Ardekani BA et al (2009) Evaluation of 14 nonlinear deformation algorithms applied to human brain MRI registration. NeuroImage 46(3):786–802. https://doi.org/10.1016/j.neuroimage.2008.12.037

    Article  PubMed  PubMed Central  Google Scholar 

  59. Eickhoff SB, Stephan KE, Mohlberg H et al (2005) A new SPM toolbox for combining probabilistic cytoarchitectonic maps and functional imaging data. NeuroImage 25(4):1325–1335. https://doi.org/10.1016/j.neuroimage.2004.12.034

    Article  PubMed  Google Scholar 

  60. Ashburner J (2009) Computational anatomy with the SPM software. Magn Reson Imaging 27(8):1163–1174. https://doi.org/10.1016/j.mri.2009.01.006

    Article  PubMed  Google Scholar 

  61. Boyes RG, Rueckert D, Aljabar P et al (2006) Cerebral atrophy measurements using Jacobian integration: comparison with the boundary shift integral. NeuroImage 32(1):159–169. https://doi.org/10.1016/j.neuroimage.2006.02.052

    Article  PubMed  Google Scholar 

  62. Malone IB, Leung KK, Clegg S et al (2015) Accurate automatic estimation of total intracranial volume: a nuisance variable with less nuisance. NeuroImage 104:366–372. https://doi.org/10.1016/j.neuroimage.2014.09.034

    Article  PubMed  PubMed Central  Google Scholar 

  63. Avants BB, Epstein CL, Grossman M et al (2008) Symmetric diffeomorphic image registration with cross-correlation: evaluating automated labeling of elderly and neurodegenerative brain. Med Image Anal 12(1):26–41. https://doi.org/10.1016/j.media.2007.06.004

    Article  CAS  PubMed  Google Scholar 

  64. Callaert DV, Ribbens A, Maes F et al (2014) Assessing age-related gray matter decline with voxel-based morphometry depends significantly on segmentation and normalization procedures. Front Aging Neurosci 6:124. https://doi.org/10.3389/fnagi.2014.00124

    Article  PubMed  PubMed Central  Google Scholar 

  65. Shen Q, Zhao W, Loewenstein DA et al (2012) Comparing new templates and atlas-based segmentations in the volumetric analysis of brain magnetic resonance images for diagnosing Alzheimer's disease. Alzheimers Dement 8(5):399–406. https://doi.org/10.1016/j.jalz.2011.07.002

    Article  PubMed  Google Scholar 

  66. Eggert LD, Sommer J, Jansen A et al (2012) Accuracy and reliability of automated gray matter segmentation pathways on real and simulated structural magnetic resonance images of the human brain. PLoS One 7(9):e45081. https://doi.org/10.1371/journal.pone.0045081

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Gaser C (2009) Partial volume segmentation with adaptive maximum a posteriori (MAP) approach. NeuroImage 47:S121. https://doi.org/10.1016/s1053-8119(09)71151-6

    Article  Google Scholar 

  68. Voevodskaya O, Simmons A, Nordenskjold R et al (2014) The effects of intracranial volume adjustment approaches on multiple regional MRI volumes in healthy aging and Alzheimer's disease. Front Aging Neurosci 6:264. https://doi.org/10.3389/fnagi.2014.00264

    Article  PubMed  PubMed Central  Google Scholar 

  69. Boban M, Kostovic I, Simic G (2006) Nucleus subputaminalis: neglected part of the basal nucleus of Meynert. Brain 129(Pt 4):E42.; author reply E43. https://doi.org/10.1093/brain/awl025

    Article  PubMed  Google Scholar 

  70. Schliebs R, Arendt T (2006) The significance of the cholinergic system in the brain during aging and in Alzheimer’s disease. J Neural Transm 113(11):1625–1644. https://doi.org/10.1007/s00702-006-0579-2

    Article  CAS  PubMed  Google Scholar 

  71. Rogers JD, Brogan D, Mirra SS (1985) The nucleus basalis of Meynert in neurological disease: a quantitative morphological study. Ann Neurol 17(2):163–170. https://doi.org/10.1002/ana.410170210

    Article  CAS  PubMed  Google Scholar 

  72. Samuel W, Terry RD, DeTeresa R et al (1994) Clinical correlates of cortical and nucleus basalis pathology in Alzheimer dementia. Arch Neurol 51(8):772–778

    Article  CAS  PubMed  Google Scholar 

  73. Iraizoz I, Guijarro JL, Gonzalo LM et al (1999) Neuropathological changes in the nucleus basalis correlate with clinical measures of dementia. Acta Neuropathol 98(2):186–196

    Article  CAS  PubMed  Google Scholar 

  74. Grothe MJ, Schuster C, Bauer F et al (2014) Atrophy of the cholinergic basal forebrain in dementia with Lewy bodies and Alzheimer's disease dementia. J Neurol 261(10):1939–1948. https://doi.org/10.1007/s00415-014-7439-z

    Article  PubMed  Google Scholar 

  75. Arendt T, Bigl V, Arendt A et al (1983) Loss of neurons in the nucleus basalis of Meynert in Alzheimer's disease, paralysis agitans and Korsakoff's disease. Acta Neuropathol 61(2):101–108

    Article  CAS  PubMed  Google Scholar 

  76. Teipel S, Raiser T, Riedl L et al (2016) Atrophy and structural covariance of the cholinergic basal forebrain in primary progressive aphasia. Cortex 83:124–135. https://doi.org/10.1016/j.cortex.2016.07.004

    Article  PubMed  Google Scholar 

  77. Wolf D, Grothe M, Fischer FU et al (2014) Association of basal forebrain volumes and cognition in normal aging. Neuropsychologia 53:54–63. https://doi.org/10.1016/j.neuropsychologia.2013.11.002

    Article  CAS  PubMed  Google Scholar 

  78. Olesen OF, Dago L, Mikkelsen JD (1998) Amyloid beta neurotoxicity in the cholinergic but not in the serotonergic phenotype of RN46A cells. Brain Res Mol Brain Res 57(2):266–274

    Article  CAS  PubMed  Google Scholar 

  79. Zheng WH, Bastianetto S, Mennicken F et al (2002) Amyloid beta peptide induces tau phosphorylation and loss of cholinergic neurons in rat primary septal cultures. Neuroscience 115(1):201–211

    Article  CAS  PubMed  Google Scholar 

  80. Boncristiano S, Calhoun ME, Kelly PH et al (2002) Cholinergic changes in the APP23 transgenic mouse model of cerebral amyloidosis. J Neurosci 22(8):3234–3243. doi:20026314

    CAS  PubMed  Google Scholar 

  81. Bell KF, Ducatenzeiler A, Ribeiro-da-Silva A et al (2006) The amyloid pathology progresses in a neurotransmitter-specific manner. Neurobiol Aging 27(11):1644–1657. https://doi.org/10.1016/j.neurobiolaging.2005.09.034

    Article  CAS  PubMed  Google Scholar 

  82. Nitsch RM, Slack BE, Wurtman RJ et al (1992) Release of Alzheimer amyloid precursor derivatives stimulated by activation of muscarinic acetylcholine receptors. Science 258(5080):304–307

    Article  CAS  PubMed  Google Scholar 

  83. Ramos-Rodriguez JJ, Pacheco-Herrero M, Thyssen D et al (2013) Rapid beta-amyloid deposition and cognitive impairment after cholinergic denervation in APP/PS1 mice. J Neuropathol Exp Neurol 72(4):272–285. https://doi.org/10.1097/NEN.0b013e318288a8dd

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Kolisnyk B, Al-Onaizi M, Soreq L et al (2016) Cholinergic surveillance over hippocampal RNA metabolism and Alzheimer's-like pathology. Cereb Cortex. https://doi.org/10.1093/cercor/bhw177

  85. Ovsepian SV, Herms J (2013) Drain of the brain: low-affinity p75 neurotrophin receptor affords a molecular sink for clearance of cortical amyloid beta by the cholinergic modulator system. Neurobiol Aging 34(11):2517–2524. https://doi.org/10.1016/j.neurobiolaging.2013.05.005

    Article  CAS  PubMed  Google Scholar 

  86. Anaclet C, Pedersen NP, Ferrari LL et al (2015) Basal forebrain control of wakefulness and cortical rhythms. Nat Commun 6:8744. https://doi.org/10.1038/ncomms9744

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Lim YY, Maruff P, Schindler R et al (2015) Disruption of cholinergic neurotransmission exacerbates Abeta-related cognitive impairment in preclinical Alzheimer's disease. Neurobiol Aging 36(10):2709–2715. https://doi.org/10.1016/j.neurobiolaging.2015.07.009

    Article  CAS  PubMed  Google Scholar 

  88. Teipel SJ, Bruno D, Grothe MJ et al (2015) Hippocampus and basal forebrain volumes modulate effects of anticholinergic treatment on delayed recall in healthy older adults. Alzheimers Dement (Amst) 1(2):216–219. https://doi.org/10.1016/j.dadm.2015.01.007

    Google Scholar 

  89. Kendziorra K, Wolf H, Meyer PM et al (2011) Decreased cerebral alpha4beta2* nicotinic acetylcholine receptor availability in patients with mild cognitive impairment and Alzheimer's disease assessed with positron emission tomography. Eur J Nucl Med Mol Imaging 38(3):515–525. https://doi.org/10.1007/s00259-010-1644-5

    Article  CAS  PubMed  Google Scholar 

  90. Bohnen NI, Muller ML, Kuwabara H et al (2009) Age-associated leukoaraiosis and cortical cholinergic deafferentation. Neurology 72(16):1411–1416. https://doi.org/10.1212/WNL.0b013e3181a187c6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Bohnen NI, Kaufer DI, Hendrickson R et al (2005) Cognitive correlates of alterations in acetylcholinesterase in Alzheimer's disease. Neurosci Lett 380(1–2):127–132. https://doi.org/10.1016/j.neulet.2005.01.031

    Article  CAS  PubMed  Google Scholar 

  92. Wolf D, Bocchetta M, Preboske GM et al (2017) Reference standard space hippocampus labels according to the EADC-ADNI harmonized protocol: utility in automated volumetry. Alzheimers Dement. https://doi.org/10.1016/j.jalz.2017.01.009

  93. Frisoni GB, Jack CR Jr, Bocchetta M et al (2015) The EADC-ADNI harmonized protocol for manual hippocampal segmentation on magnetic resonance: evidence of validity. Alzheimers Dement 11(2):111–125. https://doi.org/10.1016/j.jalz.2014.05.1756

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany

    Michel J. Grothe, Ingo Kilimann & Stefan Teipel

  2. Department of Psychosomatic Medicine, University of Rostock, Rostock, Germany

    Ingo Kilimann & Stefan Teipel

  3. Department of Neurology, University of California, San Francisco, CA, USA

    Lea Grinberg

  4. Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, Brazil

    Helmut Heinsen

  5. Department of Psychiatry, Psychosomatics and Psychotherapy, Julius-Maximilians-University, Würzburg, Germany

    Helmut Heinsen

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  1. Michel J. Grothe
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  2. Ingo Kilimann
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  4. Helmut Heinsen
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  5. Stefan Teipel
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Correspondence to Michel J. Grothe .

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  1. Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-Universität München, Munich, Germany

    Robert Perneczky

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Grothe, M.J., Kilimann, I., Grinberg, L., Heinsen, H., Teipel, S. (2018). In Vivo Volumetry of the Cholinergic Basal Forebrain. In: Perneczky, R. (eds) Biomarkers for Preclinical Alzheimer’s Disease. Neuromethods, vol 137. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7674-4_15

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  • DOI: https://doi.org/10.1007/978-1-4939-7674-4_15

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  • Print ISBN: 978-1-4939-7673-7

  • Online ISBN: 978-1-4939-7674-4

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