Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2012 Oct 1;2(10):a006296.
doi: 10.1101/cshperspect.a006296.

The genetics of Alzheimer disease

Rudolph E Tanzi  1
Affiliations
Review

The genetics of Alzheimer disease

Rudolph E Tanzi. Cold Spring Harb Perspect Med. .

Abstract

Family history is the second strongest risk factor for Alzheimer disease (AD) following advanced age. Twin and family studies indicate that genetic factors are estimated to play a role in at least 80% of AD cases. The inheritance of AD exhibits a dichotomous pattern. On one hand, rare mutations in APP, PSEN1, and PSEN2 virtually guarantee early-onset (<60 years) familial AD, which represents ∼5% of AD. On the other hand, common gene polymorphisms, such as the ε4 and ε2 variants of the APOE gene, can influence susceptibility for ∼50% of the common late-onset AD. These four genes account for 30%-50% of the inheritability of AD. Genome-wide association studies have recently led to the identification of 11 additional AD candidate genes. This paper reviews the past, present, and future attempts to elucidate the complex and heterogeneous genetic underpinnings of AD.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Potential roles of select Alzheimer disease (AD) genes in Aβ-related pathogenesis of AD. (Modified from Bertram and Tanzi 2008; reprinted with permission from the author.)
See this image and copyright information in PMC

References

    1. Andersen OM, Reiche J, Schmidt V, Gotthardt M, Spoelgen R, Behlke J, von Arnim CAF, Breiderhoff T, Jansen P, Wu X, et al. 2005. Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein. Proc Natl Acad Sci 102: 13461–13466 - PMC - PubMed
    1. Bertram L, Tanzi RE 2005. The genetic epidemiology of neurodegenerative disease. J Clin Invest 115: 1449–1457 - PMC - PubMed
    1. Bertram L, Tanzi RE 2008. Thirty years of Alzheimer’s disease genetics: Systematic meta-analyses herald a new era. Nat Rev Neurosci 9: 768–778 - PubMed
    1. Bertram L, Tanzi RE 2009. Genome-wide association studies in Alzheimer’s disease. Hum Mol Genet 18: R137–145 - PMC - PubMed
    1. Bertram L, McQueen MB, Mullin K, Blacker D, Tanzi RE 2007. Systematic meta-analyses of Alzheimer disease genetic association studies: The AlzGene database. Nat Genet 39: 17–23 - PubMed