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. 2019 Mar;7(1):1-12.
doi: 10.1007/s40142-019-0156-2. Epub 2019 Jan 24.

Protective Variants in Alzheimer's Disease

Shea J Andrews  1   2 , Brian Fulton-Howard  1   2 , Alison Goate  1
Affiliations

Protective Variants in Alzheimer's Disease

Shea J Andrews et al. Curr Genet Med Rep. 2019 Mar.

Abstract

Purpose of review: Over the last decade over 40 loci have been associated with risk of Alzheimer's disease (AD). However, most studies have either focused on identifying risk loci or performing unbiased screens without a focus on protective variation in AD. Here, we provide a review of known protective variants in AD and their putative mechanisms of action. Additionally, we recommend strategies for finding new protective variants.

Recent findings: Recent Genome-Wide Association Studies have identified both common and rare protective variants associated with AD. These include variants in or near APP, APOE, PLCG2, MS4A, MAPT-KANSL1, RAB10, ABCA1, CCL11, SORL1, NOCT, SCL24A4-RIN3, CASS4, EPHA1, SPPL2A, and NFIC.

Summary: There are very few protective variants with functional evidence and a derived allele with a frequency below 20%. Additional fine mapping and multi-omic studies are needed to further validate and characterize known variants as well as specialized genome-wide scans to identify novel variants.

Keywords: Alzheimer’s disease; SNP; genetic variants; protective.

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Conflict of interest statement

Conflict of Interest Shea J Andrews and Brian Fulton-Howard each declare no potential conflicts of interest. Alison Goate reports a grant from the NIH (NIA 1 U01 AG049508).

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