TREM2 Acts Downstream of CD33 in Modulating Microglial Pathology in Alzheimer's Disease.

ABSTRACT: The microglial receptors CD33 and TREM2 have been associated with risk for Alzheimer's disease (AD). Here, we investigated crosstalk between CD33 and TREM2. We showed that knockout of CD33 attenuated amyloid beta (Aβ) pathology and improved cognition in 5xFAD mice, both of which were abrogated by additional TREM2 knockout. Knocking out TREM2 in 5xFAD mice exacerbated Aβ pathology and neurodegeneration but reduced Iba1⁺ cell numbers, all of which could not be rescued by additional CD33 knockout. RNA-seq profiling of microglia revealed that genes related to phagocytosis and signaling (IL-6, IL-8, acute phase response) are upregulated in 5xFAD;CD33^-/- and downregulated in 5xFAD;TREM2^-/- mice. Differential gene expression in 5xFAD;CD33^-/- microglia d

SUBMITTER: Griciuc A 

PROVIDER: S-EPMC6728215 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature