Microglia: The Brain’s Hidden Allies in the Fight Against Alzheimer’s

• A groundbreaking study has uncovered how microglia , the brain’s immune cells, play a protective role in slowing the progression of Alzheimer’s disease . These findings provide crucial insight into immune-based therapies that could target the root causes of neurodegenerative disorders rather than just managing symptoms.

Microglia as Brain Protectors

• Microglia are specialised immune cells responsible for maintaining brain health by removing waste and regulating inflammation. Researchers have now identified a specific subset of microglia that can counteract Alzheimer’s-related damage . These cells exhibit low levels of PU.1 , a transcription factor, and high levels of the receptor CD28 , which enhances immune regulation.
• This unique balance enables microglia to reduce inflammation and limit the buildup of amyloid plaques and tau proteins — both of which are hallmark features of Alzheimer’s disease.

Role of PU.1 and CD28 in the Brain

• PU.1, encoded by the SPI1 gene , controls gene expression in immune cells, while CD28 helps them communicate and perform regulatory functions. The study found that lowering PU.1 levels in microglia makes them behave more like lymphoid cells , enabling them to better preserve memory and cognitive function . Conversely, when CD28 was removed, inflammation worsened, confirming its importance in brain immunity.

Scientific Collaboration and Key Findings

• The study was led by Dr Anne Schaefer (Icahn School of Medicine) and Dr Alexander Tarakhovsky (Rockefeller University) , with collaboration from the Max Planck Institute and Mount Sinai’s Ronald M. Loeb Center for Alzheimer’s Disease . Their joint research demonstrated that microglia are active defenders of neural networks, not merely reactive cells.

Genetic and Therapeutic Implications

• Previous genetic studies have shown that individuals with naturally lower PU.1 levels have a reduced risk of Alzheimer’s . This new discovery strengthens the case for developing immunotherapies that modulate microglial function , offering a new direction in treating Alzheimer’s at the molecular level.

Exam-Oriented Facts

• Protective microglia: Low PU.1, high CD28 expression

• PU.1 gene: Encoded by SPI1 , linked to lower Alzheimer’s risk

• Lead institutions: Rockefeller University, Mount Sinai, Max Planck Institute

• Key finding: Modulating microglia may help slow Alzheimer’s progression