Targeting amyloid-β pathology by chimeric antigen receptor astrocyte (CARA) therapy

While recent advances in anti-amyloid immunotherapies have shown promise, their inherent limitations underscore the need for innovative therapeutic paradigms. Here, we propose novel anti-amyloid chimeric antigen receptors expressed in astrocytes (CAR-A) and confirm their functionality in vitro.

We further demonstrate the in vivo effectiveness of two designs in reducing amyloid plaque accumulation and related pathologies in a mouse model of amyloidosis. We also demonstrated the potential of CARA therapy in preventing amyloid burden and related pathologies prior to the plaque formation in the 5xFAD model. Our single nuclei analysis on pooled hippocampi showed that CAR-A treatment induced a unique glial cell response towards the amyloid pathology, reflecting that both astrocytes and microglia share the burden of amyloid aggregates.