Encyclopedia of Gerontology and Population Aging

Living Edition
| Editors: Danan Gu, Matthew E. Dupre

Alzheimer’s Disease

  • Yat-Fung Shea
  • Steven T. DeKoskyEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-3-319-69892-2_665-1



Alzheimer’s disease is a chronic neurodegenerative disease characterized neuropathologically by the presence of amyloid plaques and neurofibrillary tangles.


The clinical syndrome and pathological features of Alzheimer’s disease (AD) were first described by Alois Alzheimer, a psychiatrist and neuropathologist, when he worked at the state asylum in Frankfurt, Germany, at the turn of the twentieth century (Alzheimer et al. 1995). He described the symptoms in a 51-year-old woman, Auguste Deter (Maurer 1998), who was brought to his clinic. He subsequently identified neuritic plaques, neurofibrillary tangles (NFT), and amyloid angiopathy. Alzheimer’s mentor, the great psychiatrist Emil Kraepelin, credited him and coined the term “Alzheimer’s disease” in his own Handbook of Psychiatry (Maurer 1998). The young age of his patient led AD to be regarded as a rare neurodegenerative disease of mid-life, with only occasional cases...

This is a preview of subscription content, log in to check access.


  1. 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(3):270–279.  https://doi.org/10.1016/j.jalz.2011.03.008CrossRefGoogle Scholar
  2. Alladi S, Xuereb J, Bak T et al (2007) Focal cortical presentations of Alzheimer’s disease. Brain 130(Pt 10):2636–2645.  https://doi.org/10.1093/brain/awm213CrossRefGoogle Scholar
  3. Alzheimer A et al (1995) An English translation of Alzheimer’s 1907 paper, “Uber eine eigenartige Erkankung der Hirnrinde”. Clin Anat 8(6):429–431CrossRefGoogle Scholar
  4. Alzheimer’s Association (2019) 2019 Alzheimer’s disease facts and figures. Alzheimers Dement 15:321–387CrossRefGoogle Scholar
  5. Birks J, Harvey RJ (2006) Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev 1:CD005593.  https://doi.org/10.1002/14651858.CD001190.pub2CrossRefGoogle Scholar
  6. Braak H, Del Tredici K (2015) Neuroanatomy and pathology of sporadic Alzheimer’s disease. Springer, BerlinCrossRefGoogle Scholar
  7. Chen R, Chan PT, Chu H et al (2017) Treatment effects between monotherapy of donepezil versus combination with memantine for Alzheimer disease: a meta-analysis. PLoS One 12(8):e0183586.  https://doi.org/10.1371/journal.pone.0183586CrossRefGoogle Scholar
  8. Cline EN, Bicca MA, Viola KL et al (2018) The amyloid-beta oligomer hypothesis: beginning of the third decade. J Alzheimers Dis 64(s1):S567–S610.  https://doi.org/10.3233/JAD-179941CrossRefGoogle Scholar
  9. Davies P, Maloney AJ (1976) Selective loss of central cholinergic neurons in Alzheimer’s disease. Lancet 2(8000):1403.  https://doi.org/10.1016/s0140-6736(76)91936-xCrossRefGoogle Scholar
  10. de Leon MJ, Ferris SH, George AE et al (1983) Positron emission tomographic studies of aging and Alzheimer disease. AJNR Am J Neuroradiol 4(3):568–571Google Scholar
  11. Dubois B, Feldman HH, Jacova C et al (2014) Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol 13(6):614–629.  https://doi.org/10.1016/S1474-4422(14)70090-0CrossRefGoogle Scholar
  12. Glenner GG, Wong CW (1984) Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 120(3):885–890.  https://doi.org/10.1016/s0006-291x(84)80190-4CrossRefGoogle Scholar
  13. Goate A, Chartier-Harlin MC, Mullan M et al (1991) Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature 349(6311):704–706.  https://doi.org/10.1038/349704a0CrossRefGoogle Scholar
  14. Heron M (2018) Deaths: leading causes for 2016. In: National vital statistics reports. National Center for Health Statistics, HyattsvilleGoogle Scholar
  15. Howard R, McShane R, Lindesay J et al (2015) Nursing home placement in the donepezil and memantine in moderate to severe Alzheimer’s disease (DOMINO-AD) trial: secondary and post-hoc analyses. Lancet Neurol 14(12):1171–1181.  https://doi.org/10.1016/S1474-4422(15)00258-6CrossRefGoogle Scholar
  16. Ittner A, Chua SW, Bertz J et al (2016) Site-specific phosphorylation of tau inhibits amyloid-beta toxicity in Alzheimer’s mice. Science 354(6314):904–908.  https://doi.org/10.1126/science.aah6205CrossRefGoogle Scholar
  17. Jack CR Jr, Bennett DA, Blennow K et al (2018) NIA-AA research framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement 14(4):535–562.  https://doi.org/10.1016/j.jalz.2018.02.018CrossRefGoogle Scholar
  18. Jansen WJ, Ossenkoppele R, Knol DL et al (2015) Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis. JAMA 313(19):1924–1938.  https://doi.org/10.1001/jama.2015.4668CrossRefGoogle Scholar
  19. Jonsson T, Atwal JK, Steinberg S et al (2012) A mutation in APP protects against Alzheimer’s disease and age-related cognitive decline. Nature 488(7409):96–99.  https://doi.org/10.1038/nature11283CrossRefGoogle Scholar
  20. Jucker M, Walker LC (2013) Self-propagation of pathogenic protein aggregates in neurodegenerative diseases. Nature 501(7465):45–51.  https://doi.org/10.1038/nature12481CrossRefGoogle Scholar
  21. Katzman R (1976) Editorial: the prevalence and malignancy of Alzheimer disease. A major killer. Arch Neurol 33(4):217–218.  https://doi.org/10.1001/archneur.1976.00500040001001CrossRefGoogle Scholar
  22. Klunk WE, Engler H, Nordberg A et al (2004) Imaging brain amyloid in Alzheimer’s disease with Pittsburgh compound-B. Ann Neurol 55(3):306–319.  https://doi.org/10.1002/ana.20009CrossRefGoogle Scholar
  23. Kunkle BW, Grenier-Boley B, Sims R et al (2019) Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Abeta, tau, immunity and lipid processing. Nat Genet 51(3):414–430.  https://doi.org/10.1038/s41588-019-0358-2CrossRefGoogle Scholar
  24. Lane CA, Hardy J, Schott JM (2018) Alzheimer’s disease. Eur J Neurol 25(1):59–70.  https://doi.org/10.1111/ene.13439CrossRefGoogle Scholar
  25. Langa KM, Larson EB, Crimmins EM et al (2017) A comparison of the prevalence of dementia in the United States in 2000 and 2012. JAMA Intern Med 177(1):51–58.  https://doi.org/10.1001/jamainternmed.2016.6807CrossRefGoogle Scholar
  26. Levy-Lahad E, Wasco W, Poorkaj P et al (1995) Candidate gene for the chromosome 1 familial Alzheimer’s disease locus. Science 269(5226):973–977.  https://doi.org/10.1126/science.7638622CrossRefGoogle Scholar
  27. Livingston G, Sommerlad A, Orgeta V et al (2017) Dementia prevention, intervention, and care. Lancet 390(10113):2673–2734.  https://doi.org/10.1016/S0140-6736(17)31363-6CrossRefGoogle Scholar
  28. Maurer KMU (1998) Alzheimer: the life of a physician and the career of a disease. Columbia University Press, New YorkGoogle Scholar
  29. McKhann G, Drachman D, Folstein M et al (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s disease. Neurology 34(7):939–944.  https://doi.org/10.1212/wnl.34.7.939CrossRefGoogle Scholar
  30. 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(3):263–269.  https://doi.org/10.1016/j.jalz.2011.03.005CrossRefGoogle Scholar
  31. McShane R, Westby MJ, Roberts E et al (2006) Memantine for dementia. Cochrane Database Syst Rev (2):CD003154.  https://doi.org/10.1002/14651858.CD003154.pub6
  32. Nakamura A, Kaneko N, Villemagne VL et al (2018) High performance plasma amyloid-beta biomarkers for Alzheimer’s disease. Nature 554(7691):249–254.  https://doi.org/10.1038/nature25456CrossRefGoogle Scholar
  33. Olsson B, Lautner R, Andreasson U et al (2016) CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis. Lancet Neurol 15(7):673–684.  https://doi.org/10.1016/S1474-4422(16)00070-3CrossRefGoogle Scholar
  34. Petersen RC, Smith GE, Waring SC et al (1999) Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 56(3):303–308.  https://doi.org/10.1001/archneur.56.3.303CrossRefGoogle Scholar
  35. Sahara N, Maeda J, Ishikawa A et al (2018) Microglial activation during pathogenesis of tauopathy in rTg4510 mice: implications for the early diagnosis of tauopathy. J Alzheimers Dis 64(s1):S353–S359.  https://doi.org/10.3233/JAD-179933CrossRefGoogle Scholar
  36. Shea YF, Chu LW, Chan AO et al (2016) A systematic review of familial Alzheimer’s disease: differences in presentation of clinical features among three mutated genes and potential ethnic differences. J Formos Med Assoc 115(2):67–75.  https://doi.org/10.1016/j.jfma.2015.08.004CrossRefGoogle Scholar
  37. Sperling RA, Aisen PS, Beckett LA et al (2011) 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(3):280–292.  https://doi.org/10.1016/j.jalz.2011.03.003CrossRefGoogle Scholar
  38. St George-Hyslop P, Haines J, Rogaev E et al (1992) Genetic evidence for a novel familial Alzheimer’s disease locus on chromosome 14. Nat Genet 2(4):330–334.  https://doi.org/10.1038/ng1292-330CrossRefGoogle Scholar
  39. Strittmatter WJ, Saunders AM, Schmechel D et al (1993) Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci U S A 90(5):1977–1981.  https://doi.org/10.1073/pnas.90.5.1977CrossRefGoogle Scholar
  40. 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.  https://doi.org/10.1126/science.7058341CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of Medicine, Li Ka Shing Faculty of MedicineQueen Mary Hospital, University of Hong KongHong KongHong Kong
  2. 2.Department of Neurology and McKnight Brain InstituteUniversity of FloridaGainesvilleUSA

Section editors and affiliations

  • Adam J. Woods
    • 1
    • 2
  1. 1.Department of Clinical and Health Psychology, College of Public Health and Health Professions, Center for Cognitive Aging and MemoryMcKnight Brain Institute, University of FloridaGainesvilleUSA
  2. 2.Department of NeuroscienceUniversity of FloridaGainesvilleUSA