White matter aging drives microglial diversity

Safaiyan, Shima; Besson-Girard, Simon; Kaya, Tugberk; Cantuti-Castelvetri, Ludovico; Liu, Lu; Ji, Hao; Schifferer, Martina; Gouna, Garyfallia; Usifo, Fumere; Kannaiyan, Nirmal; Fitzner, Dirk; Xiang, Xianyuan; Rossner, Moritz J.; Brendel, Matthias; Gokce, Ozgun und Simons, Mikael (2021): White matter aging drives microglial diversity. In: Neuron, Bd. 109, Nr. 7

Abstract

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin ; Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0896-6273
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198