Astrocytes engineered to fight Alzheimer's plaques.

Alzheimer's disease (AD) remains elusive to treat despite extensive knowledge of its pathological hallmarks. In AD, amyloid-β (Aβ) aggregates into extracellular plaques, and this aggregation is thought to ignite a pathological cascade leading to brain inflammation, intraneuronal tau protein aggregation, and, ultimately, neuronal loss. Because Aβ aggregation is a primary driver of AD pathogenesis, therapeutic strategies, including monoclonal antibodies, have focused on clearing brain Aβ. Yet clinical trials of these antibodies have yielded only modest benefits, accompanied by safety concerns that limit broad clinical adoption (1–3). On page 1006 of this issue, Chen et al. (4) report a promising alternative--engineering brain astrocytes to express chimeric antigen receptors (CARs) that enable them to target and phagocytose (engulf) A?. This astrocytebased CAR approach offers a new, "living drug" paradigm for improved safety and efficacy of AD therapeutics. [ABSTRACT FROM AUTHOR]