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The Putative Role of Red Blood Cell CR1 levels in Amyloid Beta Clearance and Alzheimer’s Disease Pathogenesis.
Funding to date:
The immune system uses complement proteins and receptors to “coat and clear” pathogens and proteins from the body. Complement Receptor 1 (CR1/CD35) is found on the surface of red blood cells in humans and helps shuttle cellular debris to the liver for degradation. Recently, specific genetic variations, called polymorphisms, in the CR1 gene were found to be associated with an increased risk of late-onset Alzheimer’s disease. We hypothesize that people with AD-risk CR1polymorphisms have low levels of CR1 protein on their red blood cells and therefore, are less efficient at clearing amyloid-â protein (Aâ) throughout life, gradually leading to Aâ aggregation and deposition in the brain. To test this hypothesis, we will examine Aâ and CR1 in archived human brain and measure the amount of CR1 molecules on red blood cells in individuals with and without AD-risk CR1polymorphisms.