Journal
ALZHEIMERS & DEMENTIA
Volume 15, Issue 12, Pages 1612-1623Publisher
WILEY
DOI: 10.1016/j.jalz.2019.05.011
Keywords
Alzheimer's disease; Resilience; APOE e4 homozygotes; CASP7; SERPINA3; Genetic resilience
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Funding
- Australian Government Research Training Program Scholarship (University of Melbourne) [96756]
- Yulgilbar Alzheimer Research Program
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Introduction: Individuals with homozygosity for the apolipoprotein E (APOE) E4 allele are in the highest risk category for late-onset Alzheimer's disease (LOAD). However, some individuals in this category do not develop LOAD beyond the age of 75 years, despite being at elevated genetic risk. These resilient individuals may carry protective genetic factors. Methods: This study aimed to systematically review any previous studies that involved resilient APOE epsilon 4 homozygotes and to identify possible modifying or protective genetic factors. Results: Fifteen studies met our inclusion criteria and reported genetic factors contributing to reduced risk. We found that only two single nucleotide polymorphisms, CASP7 rs10553596 and SERPINA3 rs4934-A/A, had strong evidence. Discussion: We found a paucity of studies adequately designed to discover protective genetic factors against LOAD. Many studies combined APOE E4 homozygotes and heterozygotes together because of small sample sizes and used control populations too young to be clearly defined as controls for LOAD. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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