Chimeric Phagocytic Receptors (CPR) to target Alzheimer’s disease pathology

Based on the premise that protein aggregation and accumulation in AD and many other neurodegenerative disorders is a key, causal, pathologic event, therapeutic strategies need to focus on i) prevention of aggregate formation ii) enhancement of clearance of the aggregate or iii) neutralization of “toxic” signaling by the aggregate. Enhancing clearance of the target protein via phagocytic mechanisms is the most direct way to test the hypothesis that enhancing clearance will be beneficial. We cloned two novel chimeric phagocytic receptors (CPRs), fused to a previously characterized anti‐Abeta scFv. The present work aims to explore whether astrocyte expressed CPRs targeting Aβ enhance phagocyte clearance and alter the target pathology, when delivered into the brain of the Alzheimer’s disease mouse model, CRND8, as a prevention paradigm, before the pathology develops, or after amyloid aggregation already occurred.