Alzheimer¡¯s Disease Risk Gene CD33 Inhibits Microglial Uptake of Amyloid Beta

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• 作者：Ana Griciuc¹ ; Alberto Serrano-Pozo² ; Antonio R. Parrado¹ ; Andrea N. Lesinski¹ ; Caroline N. Asselin¹ ; Kristina Mullin¹ ; Basavaraj Hooli¹ ; Se Hoon Choi¹ ; Bradley T. Hyman² ; Rudolph E. Tanzi¹ ; ^{tanzi@helix.mgh.harvard.edu}
• 刊名：Neuron
• 出版年：2013
• 出版时间：22 May, 2013
• 年：2013
• 卷：78
• 期：4
• 页码：631-643
• 全文大小：2876 K

文摘

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Summary

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¦Â42) levels in AD brain. Furthermore, the numbers of CD33-immunoreactive microglia were positively correlated with insoluble A¦Â42 levels and plaque burden in AD brain. CD33 inhibited uptake and clearance of A¦Â42 in microglial cell cultures. Finally, brain levels of insoluble A¦Â42 as well as amyloid plaque burden were markedly reduced in APP_Swe/PS1_¦¤E9/CD33^?/? mice. Therefore, CD33 inactivation mitigates A¦Â pathology and CD33 inhibition could represent a novel therapy for AD.

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