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

Area of Science:

• Neuroscience
• Immunology
• Genetics

Background:

• Genome-wide association studies (GWAS) link the complement cascade, particularly complement receptor 1 (CR1), to Alzheimer's disease (AD) risk.
• The precise role of CR1 in AD pathogenesis is unclear, partly due to controversy regarding its expression in the brain.

Purpose of the Study:

• To definitively establish the expression of CR1 in the human brain at both mRNA and protein levels.
• To investigate whether CR1 expression differs between Alzheimer's disease and control brains.

Main Methods:

• Assessed CR1 expression using immunostaining and Western blotting in human microglial cell lines and induced pluripotent stem cell (iPSC)-derived microglia.
• Analyzed CR1 mRNA and protein levels in post-mortem brain tissue from AD and control donors.
• Utilized validated CR1-specific antibodies and assessed co-localization with glial markers.

Main Results:

• CR1 protein and mRNA were detected in cultured human microglia and iPSC-derived microglia.
• CR1 protein was found in both control and AD human brains, co-localizing with microglia and astrocytes.
• Significantly increased CR1 protein and mRNA expression was observed in AD brains compared to controls.

Conclusions:

• The study unequivocally demonstrates CR1 expression in human brain microglia and astrocytes.
• Findings support the hypothesis that CR1 variants influence AD risk through direct effects on glial cell function within the brain.