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Protective Variants in Alzheimer’s Disease

  • Neurogenetics and Psychiatric Genetics (C Cruchaga and C Karch, Section Editors)
  • Published:
Current Genetic Medicine Reports Aims and scope Submit manuscript

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.

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  1. Shea J. Andrews and Brian Fulton-Howard contributed equally to this work.

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  1. Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY, USA

    Shea J. Andrews, Brian Fulton-Howard & Alison Goate

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Shea J Andrews and Brian Fulton-Howard each declare no potential conflict of interest.

Alison Goate reports a grant from the NIH (NIA 1 U01 AG049508).

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Supplementary Table 1:

Reported Protective variants for Alzheimer's disease identified in our literature search. (XLSX 100 kb)

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Andrews, S.J., Fulton-Howard, B. & Goate, A. Protective Variants in Alzheimer’s Disease. Curr Genet Med Rep 7, 1–12 (2019). https://doi.org/10.1007/s40142-019-0156-2

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