Nature medicine

Cell responses linked to TREM2 and other pathways in Alzheimer's disease from human and mouse brain cell analysis

Updated

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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Funding

Competing interests

Competing Interests Statement. M. Colonna receives research support from Pfizer, Amgen, Alector and Ono.
PubMed

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