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Complement receptor 1 is expressed on brain cells and in the human brain

Daskoulidou, Nikoleta, Shaw, Bethany, Torvell, Megan, Watkins, Lewis, Cope, Emma L., Carpanini, Sarah M., Allen, Nicholas D. ORCID: and Morgan, B. Paul ORCID: 2023. Complement receptor 1 is expressed on brain cells and in the human brain. Glia 71 (6) , pp. 1522-1535. 10.1002/glia.24355

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Genome wide association studies (GWAS) have highlighted the importance of the complement cascade in pathogenesis of Alzheimer's disease (AD). Complement receptor 1 (CR1; CD35) is among the top GWAS hits. The long variant of CR1 is associated with increased risk for AD; however, roles of CR1 in brain health and disease are poorly understood. A critical confounder is that brain expression of CR1 is controversial; failure to demonstrate brain expression has provoked the suggestion that peripherally expressed CR1 influences AD risk. We took a multi‐pronged approach to establish whether CR1 is expressed in brain. Expression of CR1 at the protein and mRNA level was assessed in human microglial lines, induced pluripotent stem cell (iPSC)‐derived microglia from two sources and brain tissue from AD and control donors. CR1 protein was detected in microglial lines and iPSC‐derived microglia expressing different CR1 variants when immunostained with a validated panel of CR1‐specific antibodies; cell extracts were positive for CR1 protein and mRNA. CR1 protein was detected in control and AD brains, co‐localizing with astrocytes and microglia, and expression was significantly increased in AD compared to controls. CR1 mRNA expression was detected in all AD and control brain samples tested; expression was significantly increased in AD. The data unequivocally demonstrate that the CR1 transcript and protein are expressed in human microglia ex vivo and on microglia and astrocytes in situ in the human brain; the findings support the hypothesis that CR1 variants affect AD risk by directly impacting glial functions.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Additional Information: License information from Publisher: LICENSE 1: URL:
Publisher: Wiley
ISSN: 0894-1491
Date of First Compliant Deposit: 27 February 2023
Date of Acceptance: 9 February 2023
Last Modified: 21 Sep 2023 18:01

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