. New Genetic Links Between Alzheimer Disease and Immune-Mediated Diseases Revealed by Overlapping Genome-wide Association Study Hits. JAMA Neurol. 2016 Jun 1;73(6):638-40. PubMed.

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  1. It is clear that neuroimmune response is key to the genetics of Alzheimer’s disease, not just because of the identification of TREM2 as a risk locus but also from the systematic analysis of the GWAS hits (Jones et al., 2010). Interestingly, transgenic mouse work has shown that many of the GWAs hits, and TREM2, are the biggest responders to plaque deposition, and overlaying GWAS loci with the genes in the TREM2 module of co-expression shows just how important this process appears to be (Matarin et al., 2015). These genes do not respond as markedly in response to tangle deposition, suggesting perhaps that the order of events is plaque deposition, immune response, tangle deposition.

    References:

    . Genetic evidence implicates the immune system and cholesterol metabolism in the aetiology of Alzheimer's disease. PLoS One. 2010;5(11):e13950. PubMed.

    . A genome-wide gene-expression analysis and database in transgenic mice during development of amyloid or tau pathology. Cell Rep. 2015 Feb 3;10(4):633-44. Epub 2015 Jan 22 PubMed.

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  1. New Genetic Method Connects Immune Genes to Alzheimer’s