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

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…

• CA
  Cure Alzheimer's Fund
• NI
  National Institutes of Health

  Awards: P01 AG078106, R21 AG059176, RF1 AG051485