A groundbreaking study led by neuroscientists from the City University of New York (CUNY) has uncovered a key stress-related pathway, the integrated stress response (ISR), that drives nerve degeneration in Alzheimer’s disease. The researchers identified “dark microglia,” specialized immune cells that, under stress, release harmful lipids damaging synaptic connections and neuron communication. Using brain scans and electron microscopy, the team discovered that brains affected by Alzheimer’s harbored twice as many stressed microglia as healthy brains. Blocking the ISR pathway in mouse models not only prevented synaptic damage but also reduced the toxic buildup of tau proteins—two hallmarks of Alzheimer’s. These findings reveal a critical link between cellular stress and neurotoxicity, offering hope for new treatments targeting harmful microglial phenotypes or lipid production. Further research could lead to therapies that halt or reverse Alzheimer’s progression, providing relief to millions of patients and their families worldwide.
Source: https://www.cell.com/neuron/abstract/S0896-6273(24)00875-4
