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


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
StatePublished - Dec 15 2014


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

ASJC Scopus subject areas

  • Medicine(all)


Dive into the research topics of 'Genetics of Alzheimer Disease'. Together they form a unique fingerprint.

Cite this