Original story: Texas Public Radio
By: Bonnie Petrie
(December 7, 2025) — When a person has Alzheimer’s disease, a protein called amyloid accumulates to form sticky globs called plaques outside of brain cells. Abnormal tau proteins create twisted fibers inside neurons. Alzheimer’s researchers have spent a lot of time learning about how these proteins clump and tangle. “But they are largely ignoring the lipids,” said UT Health San Antonio neuroscientist Juan Pablo Palavicini, PhD, “Which, in my view, is a big mistake, because they make up more than half of the dry weight of the brain.”
Palavicini is an assistant professor in the Department of Cellular and Integrative Physiology at the Joe R. and Teresa Lozano Long School of Medicine and a researcher with the Sam and Ann Barshop Institute for Longevity and Aging Studies at The University of Texas at San Antonio. He explained that changes in certain brain lipids — which are types of fat — play a major role in Alzheimer’s disease. Palavicini and his Barshop colleague Xianlin Han, PhD co-led a study in collaboration with the University of California at Irvine which discovered that cells called microglia can drive lipid abnormalities.
”Microglia are the immune cells of the brain. Their number one role is if there’s any debris out there, they will clear it,” Palavicini said.
Normal physiological functions of the brain create this debris, and when a brain is functioning well, microglia work like janitors at a school. Kids make a mess, breaking things and leaving debris around. The janitor goes from mess to mess, cleaning them up. “You get some mild debris that they have to gobble up and clear, and they become a little bit inflammatory,” Palavicini explained. “But then they come back to their resting state.”
As we age, microglia are tasked with recycling more debris, more often, and it becomes difficult to keep up. In the context of Alzheimer’s disease, they can’t.
“We have so much debris and so chronically that the microglia initially try to clear it, but eventually they become so saturated, and they just exhaust,” Palavicini said.
When microglia are exhausted, they stop working. But that’s not all that happens.
“Instead of being the good guys that were helping us to clear the debris, they become bad guys and just start releasing inflammatory stimuli,” he said. “And this generates a cascade of negative events.”
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