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While the precise pathophysiology of AD is incompletely understood, clinical trials of antibodies targeting aggregated forms of \u03b2 amyloid (A\u03b2) have shown that reducing amyloid plaques can mitigate cognitive decline in patients with early-stage AD. Here, we describe what we believe to be a novel approach to target and degrade amyloid plaques by genetically engineering macrophages to express an A\u03b2-targeting chimeric antigen receptor (CAR-Ms). When injected intrahippocampally, first-generation CAR-Ms have limited persistence and fail to significantly reduce plaque load, which led us to engineer next-generation CAR-Ms that secrete M-CSF and self-maintain without exogenous cytokines. Cytokine secreting \u201creinforced CAR-Ms\u201d have greater survival in the brain niche and significantly reduce plaque load locally in vivo. 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