Researchers have identified a newly discovered type of brain cell that may help shield the brain from Alzheimer’s disease by reducing inflammation and slowing disease progression — a finding that could open doors to novel treatment approaches.
The international study, published on November 5 in Nature, was led by scientists from the Icahn School of Medicine at Mount Sinai in collaboration with the Max Planck Institute for Biology and Ageing (Germany), The Rockefeller University, The City University of New York, and other partners.
Alzheimer’s disease, the most common cause of dementia, involves the dysfunction of microglia — the brain’s immune cells that can either protect against or contribute to neurodegeneration. The research team discovered a unique subset of microglia with reduced levels of a transcription factor called PU.1 and elevated expression of the receptor CD28. These specialized microglia appear to calm inflammation, reduce amyloid plaque buildup, and limit the spread of toxic tau proteins — two hallmarks of Alzheimer’s.
Using mouse models and human brain tissues, the scientists demonstrated that lowering PU.1 levels reprograms microglia to express immune-regulating receptors typically found in lymphoid cells. Although these protective cells represent only a small portion of total microglia, their influence is significant — they help suppress widespread inflammation and preserve memory function in mice.
Further experiments showed that removing CD28 from this subset of microglia worsened inflammation and accelerated plaque accumulation, confirming the receptor’s critical role in maintaining brain-protective activity.
The research expands upon earlier genetic findings by Alison M. Goate, DPhil, Jean C. and James W. Crystal Professor of Genomics and Chair of the Department of Genetics and Genomic Sciences at the Icahn School of Medicine, founding director of the Ronald M. Loeb Center for Alzheimer's Disease at Mount Sinai, and a senior co-author of the study. Dr. Goate's prior work identified a common genetic variant in SPI1 (the gene responsible for producing PU.1) that is linked to a lower risk of developing Alzheimer's disease.