Chimeric Antigen Receptor Cell Therapy: Current Status and Its Potential in Aging and Alzheimer's Disease.

With an aging population, there is a worldwide increase in the prevalence of neurodegenerative diseases. Alzheimer's disease (AD) is the most prevalent form of dementia. Research focusing on aging has revealed a time-related accumulation of senescent cells that escape the cell cycle but remain metabolically active and spread the senescent traits to neighboring cells via the senescence-associated secretory phenotype. The accumulated senescent cells in various tissues are involved in the pathogenesis of several age-related conditions. As such, eliminating them would be an appealing anti-aging strategy. Following the high success rates of engineered chimeric antigen receptor (CAR)-T cells in hematological malignancies, the scientific community has tried to adapt the strategy to fight aging and age-related diseases. Research in this area is only in its infancy, but the results obtained from in vitro and animal models are encouraging. Due to the serious side effects of CAR-T cell therapies (cytokine release syndrome, immune cell-associated neurological syndrome) and because in AD the elimination of neurons with neurofibrillary tangles and amyloid aggregates should be avoided (given the limited regenerative potential of these cells), CAR macrophages, CAR regulatory T cells, or exosomes derived from these cells are a more promising approach.