Alzheimer’s: Microglia’s Role in Tau Spread & Potential New Treatments
SAN ANTONIO – A researcher at UT Health San Antonio has been awarded a $402,500 grant from the Cure Alzheimer’s Fund to investigate the complex role of microglia, the brain’s resident immune cells, in the progression of Alzheimer’s disease. The two-year grant, announced February 20, 2026, will support the work of Sarah C. Hopp, PhD, associate professor of pharmacology with the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases and the South Texas Alzheimer’s Disease Research Center.
Dr. Hopp’s research focuses on a seeming paradox: although microglia typically protect the brain by clearing debris and repairing damage, growing evidence suggests they may also contribute to the spread of toxic tau proteins, a hallmark of Alzheimer’s disease. The study will examine how microglia interact with these misfolded tau proteins and whether this interaction ultimately protects neurons or exacerbates the disease.
“Much still isn’t known about how [tau] spreads or what role the brain’s immune system plays in the process,” according to a paper published on the CureAlz website outlining Dr. Hopp’s upcoming study, titled “How Do Microglia Contribute to the Spread of Tau Pathology in Alzheimer’s Disease?” Toxic forms of tau act as a “lousy influence,” causing healthy tau proteins to misfold, triggering a chain reaction that spreads throughout the brain.
Dr. Hopp’s team has already identified key cellular mechanisms involved in how microglia internalize tau and the control points that determine whether the cells destroy the protein or release it back into the brain. Their research indicates that only about one-quarter of microglia actually take up misfolded tau. This subpopulation exhibits a unique genetic signature linked to endocytosis, lysosomal stress, and migration.
Experiments have shown that when microglia ingest too much tau, their ability to properly digest it breaks down, leading to the release of inflammatory signals and potentially spreading the pathology. The team also discovered that the LRP1 receptor is crucial for tau uptake, with its removal significantly reducing the amount of tau internalized by microglia.
Starting this month, Dr. Hopp’s lab will pursue three primary aims. First, they will use advanced gene-expression mapping, human stem-cell-derived microglia, and postmortem Alzheimer’s disease brain tissue to identify what makes certain microglia more likely to engulf tau than others. Second, they will investigate how microglia transition from being tau cleaners to tau spreaders, focusing on microglial migration and the lysosomal recycling system. Finally, they will test whether blocking tau uptake through the LRP1 receptor slows or prevents the spread of tau in engineered mice lacking the receptor.
The Cure Alzheimer’s Fund, a nonprofit organization dedicated to funding research aimed at preventing, slowing, or reversing Alzheimer’s disease, awarded the grant based on the potential of Dr. Hopp’s work to clarify whether microglia act as barriers or accelerators in the disease process. The findings could pave the way for new treatments designed to maintain microglia’s protective function and prevent the spread of toxic proteins.