Microglia as Brain Protectors
Researchers have identified a subset of microglia that play a protective role against Alzheimer’s pathology. These cells, when exhibiting lower levels of a protein called PU.1 and higher levels of the receptor CD28, were found to reduce inflammation and restrict the accumulation of amyloid plaques and toxic tau proteins — both key markers of Alzheimer’s.
Role of PU.1 and CD28 in the Brain
PU.1 is a transcription factor that determines which genes are activated in immune cells, while CD28 is a receptor that helps immune cells communicate and function effectively. The study showed that reducing PU.1 levels in microglia encouraged them to behave more like lymphoid cells — specialised immune regulators. This transformation enhanced their ability to preserve memory and brain health in mouse models and human tissue studies.
Scientific Collaboration and Findings
The research was led by Dr Anne Schaefer of the Icahn School of Medicine and Dr Alexander Tarakhovsky of Rockefeller University, with contributions from the Max Planck Institute and Mount Sinai’s Ronald M Loeb Center for Alzheimer’s Disease. Their findings demonstrate that microglia are not merely reactive cells but can actively protect neural circuits. Removing CD28 from these microglia worsened inflammation, confirming its central role in disease regulation.
Exam Oriented Facts
- Microglia with reduced PU.1 and increased CD28 levels protect against Alzheimer’s.
- PU.1 is encoded by the SPI1 gene, linked to lower Alzheimer’s risk.
- Researchers involved include teams from Rockefeller University and Mount Sinai.
Genetic and Therapeutic Implications
The study builds upon earlier genetic research showing that individuals with naturally lower PU.1 levels have a reduced risk of developing Alzheimer’s. This new mechanistic understanding supports the development of immune-based therapies targeting microglial function. Scientists believe this could pave the way for innovative treatments aimed at modifying the disease’s progression rather than merely alleviating its symptoms.
