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Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer’s disease
Cell responses linked to TREM2 and other pathways in Alzheimer's disease from human and mouse brain cell analysis
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Abstract
Variants of the microglia receptor TREM2 may increase Alzheimer's disease risk.
- Activation of disease-associated microglia in mouse models of Alzheimer's disease is dependent on TREM2.
- A previously undiscovered population of oligodendrocytes reactive to Serpina3nC4b was identified in 5XFAD mice.
- Human Alzheimer's disease exhibits significantly different glial cell phenotypes compared to mouse models.
- Microglia in human Alzheimer's show a signature similar to reactive microglia associated with nerve injury.
- Oligodendrocytes in human Alzheimer's disease suggest issues with axonal myelination and adaptation to neuronal loss.
- The reactive phenotype of microglia is less pronounced in carriers of certain TREM2 variants compared to non-carriers.
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