Researchers at the CUNY Graduate Center have identified a crucial link between cellular stress and the progression of Alzheimer’s disease, focusing on harmful microglia, the brain’s immune cells. While microglia can protect the brain, certain activated microglial populations exacerbate neurodegeneration. The study, published in Neuron, highlights the integrated stress response (ISR) pathway, which prompts these harmful microglia to produce toxic lipids that damage essential brain cells like neurons and oligodendrocyte progenitors.
Notably, the researchers discovered that "dark microglia," associated with cellular stress, were found in significantly higher numbers in Alzheimer’s patients compared to healthy individuals. By inhibiting the ISR or lipid synthesis in mouse models, the research team prevented synapse loss and accumulation of neurodegenerative tau proteins, indicating potential therapeutic avenues.
This study emphasizes the feasibility of developing treatments that target these harmful microglial populations or their stress-induced mechanisms, potentially halting or reversing Alzheimer’s progression. These findings offer renewed hope for patients and their families and represent a significant advancement in our understanding of the disease’s cellular mechanisms.
