Alzheimer’s could be reversed, say researchers as study finds cellular mechanism behind it

A study published in the journal Neuron has found the cellular mechanism that links stress in the brain to the progression of Alzheimer’s disease. This breakthrough can promise a major boost in the treatment of the disease.
Researchers with the Advanced Science Research Center at the CUNY Graduate Center (CUNY ASRC) have highlighted microglia, the brain’s primary immune cells, as central players in both the protective and harmful responses associated with Alzheimer’s disease, which is a progressive neurodegenerative disorder that primarily affects memory, thinking, and behavior. It is the most common cause of dementia, often beginning with mild memory loss and advancing to severe cognitive and functional impairment. The condition is characterized by the accumulation of amyloid plaques and tau tangles in the brain, leading to neuronal damage and brain shrinkage.
“We set out to answer what are the harmful microglia in Alzheimer’s disease and how can we therapeutically target them,” said Pinar Ayata, the study’s principal investigator and a professor with the CUNY ASRC Neuroscience Initiative and the CUNY Graduate Center’s Biology and Biochemistry programs. “We pinpointed a novel neurodegenerative microglia phenotype in Alzheimer’s disease characterized by a stress-related signaling pathway.”
The research team found that activating the integrated stress response (ISR) triggers microglia to produce and release toxic lipids. These lipids harm neurons and oligodendrocyte progenitor cells—two critical cell types for brain function that are most affected in Alzheimer’s disease. In preclinical models, blocking either the stress response or the lipid synthesis pathway successfully reversed Alzheimer’s disease symptoms.
According to Anna Flury, a member of Ayata’s lab and a Ph.D. student with the CUNY Graduate Center’s Biology Program, these findings reveal a critical link between cellular stress and the neurotoxic effects of microglia in Alzheimer’s disease. Targeting this pathway may open up new avenues for treatment by either halting the toxic lipid production or preventing the activation of harmful microglial phenotypes.