Hostname: page-component-78c5997874-xbtfd Total loading time: 0 Render date: 2024-11-15T02:05:48.427Z Has data issue: false hasContentIssue false
  • English
  • Français

Alzheimer Disease: Perspectives from Epidemiology and Genetics

Published online by Cambridge University Press:  01 January 2021

Jonathan L. Haines
Get access Rights & Permissions [Opens in a new window]

Abstract

Alzheimer disease (AD) is a huge and growing societal problem with upwards of 35% of the population over the age of 80 developing the disease. AD results in a loss of memory, the ability to make reasoned and sound decisions, and ultimately the inability to take care of oneself. AD has an impact not only on the sufferer, but their caretakers and loved ones, who must take on a costly and time-consuming burden of care. AD is found in virtually all racial and ethnic groups. Genetic influences on AD are substantial, and there has been a 30 year history of both success and failure. Mutations for rare early onset forms of the disease have been identified, but this information has not yet led to an effective treatment. Multiple common genetic variations have also been identified, and have led to new insights into the potential role of microglia cells in addition to neuronal cells in the brain. Despite intensive efforts, a significant portion of the genetic etiology of AD remains unknown and must be identified.

Type
Symposium 2 Articles
Information
Journal of Law, Medicine & Ethics , Volume 46 , Issue 3: The Medicalization of Poverty; Perspectives of Alzheimer's Disease: Ethical, Legal, and Social Issues , Fall 2018 , pp. 694 - 698
Copyright
Copyright © American Society of Law, Medicine and Ethics 2018

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Wilson, R. S. et al., “The Natural History of Cognitive Decline in Alzheimer's Disease,” Psychology and Aging 27, no. 4 (2012): 1008-1017; Barker, W. W. et al., “Relative Frequencies of Alzheimer Disease, Lewy Body, Vascular and Frontotemporal Dementia, and Hippocampal Sclerosis in the State of Florida Brain Bank,” Alzheimer Disease & Associated Disorders 16, no. 4 (2002): 203-212.Google Scholar
Hebert, L. E. et al., “Alzheimer Disease in the United States (2010-2050) Estimated Using the 2010 Census,” Neurology 80, no. 19 (2013): 1778-1783.Google Scholar
See supra note 1.Google Scholar
See supra note 3.Google Scholar
Alzheimer's Association, “2015 Alzheimer's Disease Facts and Figures,” Alzheimer's & Dementia 11, no. 3 (2015): 332-384; Langa, K. M. et al., “Out-of-Pocket Health Care Expenditures among Older Americans with Dementia,” Alzheimer Disease & Associated Disorders 18, no. 2 (2004): 90-98.Google Scholar
Bellou, V. et al., “Systematic Evaluation of the Associations between Environmental Risk Factors and Dementia: An Umbrella Review of Systematic Reviews and Meta-analyses,” Alzheimer's & Dementia 13, no. 4 (2017): 406-418.Google Scholar
See Wilson et al., supra note 1.Google Scholar
See Alzheimer's Association, supra note 5; Brookmeyer, R., Gray, S., and Kawas, C., “Projections of Alzheimer's Disease in the United States and the Public Health Impact of Delaying Disease Onset,” American Journal of Public Health 88, no. 9: (1998): 1337-1342.Google Scholar
Alzheimer, A., “Ueber eine eigenartige Erkranking der Hirnrinde,” Allegmeine Zeitschrift fur Psychiatrie 64 (1907): 146-148.Google Scholar
Sjogren, T., Sjogren, H., and Lindgren, A. G. H., “Morbus Alzheimer and Morbus Pick: Aa genetic, Clinical and Patho-anatomical Study,” Acta Psychiatrica Neurol Scandinavica 82, Suppl. (1952): 1-66.Google Scholar
Heyman, A. et al., “Alzheimer's Disease: Genetic Aspects and Associated Clinical Disorders,” Annals of Neurology 14, no. 5 (1983): 507-515; Nee, L., et al., “A Family with Histologically Confirmed Alzheimer's Disease,” Archives of Neurology 40 (1983): 203-208.Google Scholar
Bergen, A. L., “Heredity in Dementia of the Alzheimer Type,” Clinical Genetics 46 (1994): 144-149.Google Scholar
Gatz, M. et al., “Role of Genes and Environments for Explaining Alzheimer Disease,” Archives of General Psychiatry 63, no. 2 (2006): 168-174; Bergem, A. L. and Lannfelt, L., “Apolipoprotein E Type Epsilon4 Allele, Heritability and Age at Onset in Twins with Alzheimer Disease and Vascular Dementia,” Clinical Genetics 52, no. 5 (1997): 408-413.CrossRefGoogle Scholar
Lautenschlager, N. T. et al., “Risk of Dementia among Relatives of Alzheimer's Disease Patients in the MIRAGE Study: What Is in Store for the Oldest Old?” Neurology 46, no. 3 (1996): 641-650; Mayeux, R. et al., “Risk of Dementia in First-Degree Relatives of Patients with Alzheimer's Disease and Related Disorders,” Archives in Neurology 48, no. 3 (1991): 269-273.CrossRefGoogle Scholar
See Nee, et al., supra note 11.Google Scholar
Goate, A. M. et al., “Segregation of a Missense Mutation in the Amyloid Precursor Protein Gene with Familial Alzheimer's Disease,” Nature 33 (1991): 53-56.Google Scholar
St. George-Hyslop, P. H. et al., “Genetic Linkage Studies Suggest That Alzheimer's Disease Is Not a Single Homogenous Disorder,” Nature 347 (1990): 194-197.CrossRefGoogle Scholar
Sherrington, R. et al., “Cloning of a Gene Bearing Missense Mutations in Early-Onset Familial Alzheimer's Disease,” Nature 375 (1995): 754-760; Levy-Lahad, E. et al., “Candidate Gene for the Chromosome 1 familial Alzheimer's Disease Locus,” Science 269 (1995): 973-977.CrossRefGoogle Scholar
Corder, E. H. et al., “Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset Families,” Science 261, no. 5123 (1993): 921-923.Google Scholar
Corder, E. H. et al., “Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset Families,” Science 261, no. 5123 (1993): 921-923; Farrer, L. A. et al., “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, no. 16 (1997): 1349-56.CrossRefGoogle Scholar
Corder, E. H. et al., “Protective Effect of Apolipoprotein E Type 2 Allele for Late Onset Alzheimer Disease,” Nature Genetics 7, no. 2 (1994): 180-184.Google Scholar
Evans, D. A. et al., “Apolipoprotein E Epsilon 4 and Incidence of Alzheimer Disease in a Community Population of Older Persons,” JAMA 277, no. 10 (1997): 822-824; Daw, E. W., et al., “The Number of Trait Loci in Late-Onset Alzheimer Disease,” American Journal of Human Genetics 66, no. 1 (2000): 196-204.Google Scholar
See Farrer et al., supra note 20; Reitz, C. and Mayeux, R., “Genetics of Alzheimer's disease in Caribbean Hispanic and African American Populations,” Biological Psychiatry 75, no. 7 (2014): 534-541.Google Scholar
Naj, A. C. et al., “Common Variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 Are Associated with Late-Onset Alzheimer's Disease,” Nature Genetics 43, no. 5 (2011): 436-441; Lambert, J. C. et al., “Meta-analysis of 74,046 Individuals Identifies 11 New Susceptibility Loci for Alzheimer's Disease,” Nature Genetics 45, no. 12 (2013): 1452-8.Google Scholar
Id. (Lamber et al.).Google Scholar
Cruchaga, E. et al., “Rare Variants in APP, PSEN1 and PSEN2 Increase Risk for AD in Late-Onset Alzheimer's Disease Families,” PLoS One 7, no. 2 (2012): e31039; Kohli, M. A., et al., “Segregation of a Rare TTC3 Variant in an Extended Family with Late-Onset Alzheimer Disease,” Neurology Genetics 2, no. 1 (2016): e41.Google Scholar
See Goate et al., supra note 16.Google Scholar
See Sherrington et al., supra note 18.Google Scholar
See Levy-Lahad, supra note 18.Google Scholar
Kerber, R. A. et al., “A Genome-Wide Study Replicates Linkage of 3p22-24 to Extreme Longevity in Humans and Identifies Possible Additional Loci,” PLoS One 7, no. 4 (2012): e34746; Kunkle, B. W., et al., “Genome-Wide Linkage Analyses of Non-Hispanic White Families Identify Novel Loci for Familial Late-Onset Alzheimer's Disease,” Alzheimer's Dementia 12, no. 1 (2016): 2-10.Google Scholar
Manolio, T. A. et al., “Finding the Missing Heritability of Complex Diseases,” Nature 461, no. 7265 (2009): 747-753.Google Scholar
Beecham, G. W., Bis, J. C., Martin, E. R., et al., “The Alzheimer's Disease Sequencing Project: Study Design and Sample Selection,” Neurology Genetics 3, no. 5 (2017): e194.CrossRefGoogle Scholar
See Kunkle et al., supra note 28; Barral, S., et al., “Linkage Analyses in Caribbean Hispanic Families Identify Novel Loci Associated with Familial Late-Onset Alzheimer's Disease,” Alzheimer's & Dementia 11, no. 12 (2015): 1397-406.Google Scholar
Cohen, J. et al., “Low LDL Cholesterol in Individuals of African Descent Resulting from Frequent Nonsense Mutations in PCSK9,” Nature Genetics 37, no. 2 (2005): 161-5.Google Scholar
See Corder et al., supra note 21.Google Scholar
See Farrer et al., supra note 20Google Scholar
Cukier, H. N. et al., “ABCA7 Frameshift Deletion Associated with Alzheimer Disease in African Americans,” Neurology Genetics 2, no. 3 (2016): e79; Nho, K. et al., “Protective Variant for Hippocampal Atrophy Identified by Whole Exome Sequencing,” Annals of Neurology 77, no. 3 (2015): 547-552; Carrasquillo, M. M., et al., “A Candidate Regulatory Variant at the TREM Gene Cluster Associates with Decreased Alzheimer's Disease Risk and Increased TREML1 and TREM2 Brain Gene Expression,” Alzheimer's & Dementia 13, no. 6 (2016): 663-673.Google Scholar
Mez, J. et al., “Alzheimer's Disease Genetic Risk Variants beyond APOE Epsilon4 redict Mortality,” Alzheimer's & Dementia (Amst) 8 (2017): 188-195.CrossRefGoogle Scholar
Petersen, R. C. et al., “Alzheimer's Disease Neuroimaging Initiative (ADNI): Clinical Characterization,” Neurology 74, no. 3 (2010): 201-209.CrossRefGoogle Scholar
Petrella, J. R., “Neuroimaging and the earch for a cuCre for Alzheimer Disease,” Radiology 269, no. 3 (2013): 671-691.Google Scholar
Ertekin-Taner, N. et al., “Heritability of Plasma Amyloid Beta in Typical Late-Onset Alzheimer's Disease Pedigrees,” Genetic Epidemiology 21, no. 1 (2001): 19-30.CrossRefGoogle Scholar
Karran, E., Mercken, M., and De Strooper, B., “The Amyloid Cascade Hypothesis for Alzheimer's Disease: An Appraisal for the Development of Therapeutics,” Nature Reviews Drug Discovery 10, no. 9 (2011): 698-712; Graham, W. V., Bonito-Oliva, A., and Sakmar, T. P., “Update on Alzheimer's Disease Therapy and Prevention Strategies,” Annual Review of Medicine 68 (2017): 413-430.Google Scholar
Sims, R. et al., “Rare Coding Variants in PLCG2, ABI3, and TREM2 mplicate mMicroglial-Mediated Innate Immunity in Alzheimer's Disease,” Nature Genetics 49, no. 9 (2017): 1373-1384.CrossRefGoogle Scholar
See supra note 40.Google Scholar
Cummings, J. et al., “Alzheimer's Disease Drug Development Pipeline: 2017,” Alzheimer's & Dementia (N Y) 3, no. 3 (2017): 367-384.CrossRefGoogle Scholar