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June 2016

New Genetic Links Between Alzheimer Disease and Immune-Mediated Diseases Revealed by Overlapping Genome-wide Association Study Hits

Author Affiliations
  • 1Rocky Mountain Alzheimer’s Disease Center, Department of Neurology, University of Colorado Anschutz Medical Center, Aurora
  • 2Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Center, Aurora
JAMA Neurol. 2016;73(6):638-640. doi:10.1001/jamaneurol.2016.0407

In this issue of JAMA Neurology, Yokoyama et al1 provide a major intellectual and technological advance in our understanding of the relationship between the immune system and Alzheimer disease.

The successful elaboration of the pathogenic pathway to Alzheimer disease during the past 20 years reflects an essential collaboration between clinicians, biochemists, molecular biologists, cell biologists, neuroscientists, and geneticists.2 Indeed, most of the steps in the pathogenic pathway have been discovered, or at least validated, by the identification of specific gene mutations or alleles correlated with Alzheimer disease and of their protein products as key to, or significantly increasing the risk of, Alzheimer disease. For example, the discovery of mutations in the amyloid precursor protein gene (APP) in certain families firmly established β-amyloid (Aβ) peptide as playing a central role in Alzheimer disease, and mutations in the 2 presenilin genes, PS1 and PS2, reinforced that conclusion and indicated that APP processing into Aβ was specifically important.2

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