Alzheimer's disease risk gene CD33 inhibits microglial uptake of amyloid beta.

ABSTRACT: The transmembrane protein CD33 is a sialic acid-binding immunoglobulin-like lectin that regulates innate immunity but has no known functions in the brain. We have previously shown that the CD33 gene is a risk factor for Alzheimer's disease (AD). Here, we observed increased expression of CD33 in microglial cells in AD brain. The minor allele of the CD33 SNP rs3865444, which confers protection against AD, was associated with reductions in both CD33 expression and insoluble amyloid beta 42 (A?42) levels in AD brain. Furthermore, the numbers of CD33-immunoreactive microglia were positively correlated with insoluble A?42 levels and plaque burden in AD brain. CD33 inhibited uptake and clearance of A?42 in microglial cell cultures. Finally, brain levels of insoluble A?42 as well as amyloid plaque burden were markedly reduced in APP(Swe)/PS1(?E9)/CD33(-/-) mice. Therefore, CD33 inactivation mitigates A? pathology and CD33 inhibition could represent a novel therapy for AD.

SUBMITTER: Griciuc A 

PROVIDER: S-EPMC3706457 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature