Genetics of Alzheimer Disease

A. C. Naj, R. M. Carney, S. E. Hahn, M. A. Pericak-Vance, M. A. Slifer, J. L. Haines

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Alzheimer disease (AD) is the most common cause of dementia, a progressive and irreversible impairment of cognitive function. Family aggregation studies, twin studies, and segregation analysis provide substantial evidence for genetic influences in this illness, and studies to find genes contributing to AD have successfully identified many candidates. Missense mutations of the APP, PSEN1, and PSEN2 genes cause early-onset forms of AD (EOAD); however, persons with these autosomal dominant mutations constitute less than 2% of AD cases.The complexity of late-onset Alzheimer Disease (LOAD) genetics has required advanced statistical and laboratory approaches to identify candidate loci. Laboratory approaches like molecular cloning have identified some monogenic causes of AD, like the APP gene. Statistical approaches, including linkage and association studies, have been used to identify genetic risk factors, including the APOE ε4 polymorphism, which carries the strongest risk of any known variation in LOAD. More recently, genome-wide association studies (GWAS) have identified and replicated associations with approximately nine new risk genes throughout the genome. Novel approaches, such as whole-exome sequencing, may identify rare variants that cosegregate with or are associated with AD.Clinical testing for AD risk genes is controversial. The benefits of foreknowledge of disease risk must be weighed against the risks of possible discriminatory practices and the lack of effective treatment or preventive measures. Pharmacogenomic studies aim to inform future development of personalized clinical treatments based on an individual's genetic makeup, a promising direction for the future of AD patient care.

Original languageEnglish (US)
Title of host publicationReference Module in Biomedical Research
PublisherElsevier Inc.
ISBN (Print)9780128012383
DOIs
StatePublished - Dec 15 2014

Fingerprint

Inborn Genetic Diseases
Alzheimer Disease
Genes
Exome
Twin Studies
Genome-Wide Association Study
Molecular Cloning
Missense Mutation
Cognition
Dementia
Patient Care
Genome
Mutation

Keywords

  • AD
  • Alzheimer disease
  • Dementia
  • Genome-wide association studies

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Naj, A. C., Carney, R. M., Hahn, S. E., Pericak-Vance, M. A., Slifer, M. A., & Haines, J. L. (2014). Genetics of Alzheimer Disease. In Reference Module in Biomedical Research Elsevier Inc.. https://doi.org/10.1016/B978-0-12-801238-3.05583-5

Genetics of Alzheimer Disease. / Naj, A. C.; Carney, R. M.; Hahn, S. E.; Pericak-Vance, M. A.; Slifer, M. A.; Haines, J. L.

Reference Module in Biomedical Research. Elsevier Inc., 2014.

Research output: Chapter in Book/Report/Conference proceedingChapter

Naj, AC, Carney, RM, Hahn, SE, Pericak-Vance, MA, Slifer, MA & Haines, JL 2014, Genetics of Alzheimer Disease. in Reference Module in Biomedical Research. Elsevier Inc. https://doi.org/10.1016/B978-0-12-801238-3.05583-5
Naj AC, Carney RM, Hahn SE, Pericak-Vance MA, Slifer MA, Haines JL. Genetics of Alzheimer Disease. In Reference Module in Biomedical Research. Elsevier Inc. 2014 https://doi.org/10.1016/B978-0-12-801238-3.05583-5
Naj, A. C. ; Carney, R. M. ; Hahn, S. E. ; Pericak-Vance, M. A. ; Slifer, M. A. ; Haines, J. L. / Genetics of Alzheimer Disease. Reference Module in Biomedical Research. Elsevier Inc., 2014.
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