JNl: Female immune cells exacerbate brain damage in Alzheimer’s disease

Immune cells of the brain (microglia) can worsen neuronal damage in women with Alzheimer’s disease. This conclusion was reached by researchers from the University of Rochester. The findings were published in the Journal of Neuroinflammation (JNl).

Alzheimer’s disease is associated with the accumulation of amyloid plaques in the brain—sticky aggregates of the beta-amyloid protein. Microglia recognize these plaques and attempt to clear them, but in doing so can trigger inflammatory processes.

The researchers found that in female mice, when microglia come into contact with amyloid, they more strongly activate genes associated with interferons—molecules that typically play a role in antiviral defense.

Although interferons are important for immune responses, previous studies have shown that their excessive activation in the brain can increase inflammation and damage synapses—the connections between neurons. The scientists suggest that in both humans and mice, when microglia engulf amyloid plaques, they may encounter fragments of DNA or RNA and mistakenly perceive them as a viral threat, thereby triggering an interferon response.

In addition, the study showed that microglia in females leave behind larger and more irregular amyloid plaques, which destroy more neuronal connections than those observed in male brains.

“It was unexpected to see how strongly female microglia respond via interferon signaling while also engulfing more beta-amyloid,” notes first author Kalsinas-Rodriguez.

At the same time, the researchers found no link between these effects and hormonal fluctuations, pointing to deeper sex-based differences.