Targeting amyloid-β pathology by chimeric antigen receptor astrocyte (CAR-A) therapy
Summary
Alzheimer's disease (AD) is the leading cause of dementia and is characterized by progressive amyloid accumulation followed by tau-mediated neurodegeneration. Despite advances in anti-amyloid immunotherapies, important limitations remain, highlighting the need for new therapeutic strategies. Here, we introduce anti-amyloid chimeric antigen receptors expressed in astrocytes (CAR-A) and validate their function in vitro. We show that two CAR-A designs reduce amyloid and associated pathology a
Content
# Targeting amyloid-β pathology by chimeric antigen receptor astrocyte (CAR-A) therapy
*Published: 2026 Mar 5*
Alzheimer's disease (AD) is the leading cause of dementia and is characterized
by progressive amyloid accumulation followed by tau-mediated neurodegeneration.
Despite advances in anti-amyloid immunotherapies, important limitations remain,
highlighting the need for new therapeutic strategies. Here, we introduce
anti-amyloid chimeric antigen receptors expressed in astrocytes (CAR-A) and
validate their function in vitro. We show that two CAR-A designs reduce amyloid
and associated pathology after plaque formation and prevent early plaque
deposition in vivo. Single-nucleus RNA sequencing shows that CAR-A treatment
induces a distinct glial response to amyloid pathology involving coordinated
activity of astrocytes and microglia. Each construct additionally elicits
distinctive, receptor-specific effects in astrocytes or microglia. Together,
these findings support the therapeutic potential of CAR-A as a disease-modifying
strategy for AD.
DOI: 10.1126/science.ads3972