Parsing How Alzheimer’s Genetic Risk Works Through Microglia | Alz Forum

“Much of the genetic risk of Alzheimer’s disease plays out in microglia. But exactly how do risk variants change these cells? At the 14th International Conference on Alzheimer’s and Parkinson’s Diseases, held March 27–31 in Lisbon, Portugal, speakers filled in some gaps, and discussion of this question buzzed in the hallways all week. Christian Haass of the German Center for Neurodegenerative Diseases in Munich characterized progranulin as TREM2’s opposite. While mutations in TREM2 suppress microglial activation, mutations in progranulin permanently rev them up into voracious, toxin-spewing machines. Other speakers associated GWAS hits in general, and the MS4A gene cluster in particular, with hyperactive, damaging microglia. Researchers also highlighted potential therapeutic targets among microglial genes. Two talks presented evidence that suppressing the CD33 receptor can contain amyloidosis (see Part 5 in this series), while another fingered BIN1 as a key culprit in propagating phosphorylated tau.”
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