Alzheimer’s risk variant mildly altered brain immune cells in mice
Experiments in Alzheimer’s-model mice aged 18 or 24 months found that a risk variant had different effects from complete loss of the gene.
Edited by Boris Djordjevic · AgingResearch.News
Researchers experimented with aged AppNL-F mice, a model of Alzheimer’s disease, carrying a humanized Trem2 gene with the R47H variant or lacking Trem2 entirely. Trem2 helps regulate microglia, the brain’s immune cells. The researchers compared these mice with controls at 18 or 24 months.
Mice lacking Trem2 accumulated more amyloid beta 42, a protein fragment, and developed more damaged nerve-cell extensions. Mice carrying R47H did not show these increases. Their microglial gene activity responded similarly to controls, unlike the deficits seen in mice lacking Trem2. However, R47H mice had altered activity in genes involved in cellular stress responses and signaling within cells. The authors concluded that the variant caused mild changes in microglia, distinct from those caused by complete gene loss.
Why it matters
The authors argue that mice carrying the risk variant should help researchers investigate how it contributes to Alzheimer’s-related changes, rather than relying on mice lacking the gene.
Caveats
These experiments used genetically altered mice, not people. The findings do not establish how the variant affects Alzheimer’s disease in humans.
The paper
Nagasaki University
Experimental Neurology, Jun 24, 2026
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