Journal
ALZHEIMERS & DEMENTIA
Volume 12, Issue 6, Pages 733-748Publisher
WILEY
DOI: 10.1016/j.jalz.2016.01.012
Keywords
Dementia; Early-onset Alzheimer's disease; Genetics; Genome and exome sequencing; Missing genetic etiology; Molecular pathways
Categories
Funding
- Met-Life Foundation Award for Medical Research (USA)
- U.S. Army Medical Research and Material Command (USAMRMC) Research Award
- Janssen Pharmaceutica Stellar Research Project
- Belgian Science Policy Office Interuniversity Attraction Poles program, Belgium
- Alzheimer Research Foundation (SAO-FRA), Belgium
- Flemish Government initiated Flanders Impulse Program on Networks for Dementia Research (VIND), Belgium
- Flemish Government initiated Methusalem Excellence Program, Belgium
- Research Foundation Flanders (FWO), Belgium
- University of Antwerp Research Fund, Belgium
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As the discovery of the Alzheimer's disease (AD) genes, APP, PSEN1, and PSEN2, in families with autosomal dominant early-onset AD (EOAD), gene discovery in familial EOAD came more or less to a standstill. Only 5% of EOAD patients are carrying a pathogenic mutation in one of the AD genes or a apolipoprotein E (APOE) risk allele epsilon 4, most of EOAD patients remain unexplained. Here, we aimed at summarizing the current knowledge of EOAD genetics and its role in ongoing approaches to understand the biology of AD and disease symptomatology as well as developing new therapeutics. Next, we explored the possible molecular mechanisms that might underlie the missing genetic etiology of EOAD and discussed how the use of massive parallel sequencing technologies triggered novel gene discoveries. To conclude, we commented on the relevance of reinvestigating EOAD patients as a means to explore potential new avenues for translational research and therapeutic discoveries. (C) 2016 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association. This is an open access article under the CC BY-NC-ND license.
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