Salih, D;
Bayram, S;
Guelfi, MS;
Reynolds, RH;
Shoai, M;
Ryten, M;
Brenton, J;
... Escott-Price, V; + view all
(2018)
Genetic variability in response to Aβ deposition influences Alzheimer's risk.
BioRxiv: Cold Spring Harbor, NY, USA.
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Abstract
Genetic analysis of late-onset Alzheimer's disease risk has previously identified a network of largely microglial genes that form a transcriptional network. In transgenic mouse models of amyloid deposition we have previously shown that the expression of many of the mouse orthologs of these genes are co-ordinately up-regulated by amyloid deposition. Here we investigate whether systematic analysis of other members of this mouse amyloid-responsive network predicts other Alzheimer's risk loci. This statistical comparison of the mouse amyloid-response network with Alzheimer's disease genome-wide association studies identifies 5 other genetic risk loci for the disease (OAS1, CXCL10, LAPTM5, ITGAM and LILRB4). This work suggests that genetic variability in the microglial response to amyloid deposition is a major determinant for Alzheimer's risk.
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