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[210401 Àú³Î¹ßÇ¥] White matter aging drives microglial diversity

Kyujin Suh ¦¢ 2021-03-31

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44892

Journal home page for Neuron

Article
White matter aging drives microglial diversity

Highlights

scRNA-seq identifies age-dependent white matter-associated microglia (WAMs)

WAMs form nodules that are engaged in clearing degenerated myelin

WAM formation depends on TREM2 but not on APOE signaling

In mouse models of Alzheimer¡¯s disease, the WAM response occurs before DAM

Summary

Aging results in gray and white matter degeneration, but the specific microglial responses are unknown. Using single-cell RNA sequencing from white and gray matter separately, we identified white matter-associated microglia (WAMs), which share parts of the disease-associated microglia (DAM) gene signature and are characterized by activation of genes implicated in phagocytic activity and lipid metabolism. WAMs depend on triggering receptor expressed on myeloid cells 2 (TREM2) signaling and are aging dependent. In the aged brain, WAMs form independent of apolipoprotein E (APOE), in contrast to mouse models of Alzheimer¡¯s disease, in which microglia with the WAM gene signature are generated prematurely and in an APOE-dependent pathway similar to DAMs. Within the white matter, microglia frequently cluster in nodules, where they are engaged in clearing degenerated myelin. Thus, WAMs may represent a potentially protective response required to clear degenerated myelin accumulating during white matter aging and disease.




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