Genomic mechanisms in Alzheimer's disease
Bertram L, Tanzi RE. Brain Pathol. 2020 Sep;30(5):966-977.
Alzheimer's disease (AD) is the most common neurodegenerative disease and, owing to its increasing prevalence, represents one of the leading public health problems in aging populations. The molecular causes underlying the onset and progression of AD are manifold and hitherto still incompletely understood. Research over nearly four decades has clearly delineated genetics to play a crucial role in AD susceptibility, likely in concert with non-genetic factors. The field has gained considerable momentum and novel insights over the past 10 years owing to the advent and application of high-throughput genomics technologies in datasets of increasing size. In this contribution to the Mini-Symposium on the Molecular Etiology of Alzheimer's Disease, we review the current status of genomics research in AD. To this end, we scrutinize and discuss the main findings from the two largest and most current genome-wide association studies (GWAS) in the field, that is, the papers published by Jansen et al (Nat Genet 51:404–413) and Kunkle et al (Nat Genet 51:414–430). Particular focus is laid on genomics findings overlapping across both studies and on the novel insights they provide in terms of improving our understanding of the “genomic mechanisms” underlying this devastating disease.