Alzheimer’s Disease Genetics

Alzheimer’s disease (AD) is the leading cause of dementia, and each year the number of individuals suffering from its consequences continues to increase, yet current treatments only delay AD symptom progression and do not modify the underlying causes of the disease. Recently, the genetics of AD have been explored with increasing scope and intensity, revealing that while only a portion of AD is familial, genetics play a strong role even in the common, apparently sporadic cases of AD. Initially, autosomal dominant forms of AD were discovered in genes that are now considered central to the pathogenesis of the disease. Then, in the next phase of genetic discovery, apolipoprotein E (APOE) ε4 alleles were very strongly associated with AD risk; these findings and their role in the pathobiology of AD have been reviewed extensively elsewhere (Bettens et al. Lancet Neurol. 12(1):92–104, 2013). This current review discusses recent genetic directions in AD research and updates an earlier review, which detailed the biology and fundamental genetic findings in AD up to about 2009 (Bekris et al. J Geriatr Psychiatry Neurol. 23(4):213–27, 2010), by focusing on new findings in the rapidly changing landscape of AD genetic research and demonstrating that multiple complementary genetic approaches, particularly in large-scale genomic-level investigations, are leading to rapid and accelerating progress.