Alzheimer’s Disease Risk Gene CD33 Inhibits Microglial Uptake of Amyloid Beta
| Autor: | Basavaraj Hooli, Bradley T. Hyman, Caroline Asselin, Rudolph E. Tanzi, Ana Griciuc, Andrea N. Lesinski, Kristina Mullin, Alberto Serrano-Pozo, Antonio R. Parrado, Se Hoon Choi |
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| Rok vydání: | 2013 |
| Předmět: |
Amyloid beta
Transgene Matched-Pair Analysis Neuroscience(all) CD33 Sialic Acid Binding Ig-like Lectin 3 Mice Transgenic Polymorphism Single Nucleotide Article 03 medical and health sciences Mice 0302 clinical medicine Alzheimer Disease Reference Values medicine Animals Humans Genetic Predisposition to Disease RNA Messenger 030304 developmental biology Mice Knockout 0303 health sciences Innate immune system Amyloid beta-Peptides Microglia biology General Neuroscience Lectin medicine.disease Transmembrane protein 3. Good health Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Case-Control Studies Immunology biology.protein Cancer research Alzheimer's disease 030217 neurology & neurosurgery |
| Zdroj: | Neuron. 78(4):631-643 |
| ISSN: | 0896-6273 |
| DOI: | 10.1016/j.neuron.2013.04.014 |
| Popis: | SummaryThe 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 (Aβ42) levels in AD brain. Furthermore, the numbers of CD33-immunoreactive microglia were positively correlated with insoluble Aβ42 levels and plaque burden in AD brain. CD33 inhibited uptake and clearance of Aβ42 in microglial cell cultures. Finally, brain levels of insoluble Aβ42 as well as amyloid plaque burden were markedly reduced in APPSwe/PS1ΔE9/CD33−/− mice. Therefore, CD33 inactivation mitigates Aβ pathology and CD33 inhibition could represent a novel therapy for AD.Video Abstract |
| Databáze: | OpenAIRE |
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