Sulfatide deficiency-induced astrogliosis and myelin lipid dyshomeostasis are independent of TREM2-mediated microglial activation.

ABSTRACT: Disrupted lipid homeostasis and neuroinflammation often co-exist in neurodegenerative disorders, including Alzheimer's disease (AD). However, the intrinsic connection and causal relationship between these deficits remain elusive. Our previous studies show that the loss of sulfatide (ST), a class of myelin-enriched lipids, causes AD-like neuroinflammatory responses, cognitive impairment, bladder enlargement, and lipid dyshomeostasis. To better understand the relationship between neuroinflammation and lipid disruption induced by ST deficiency, we established a ST-deficient mouse model with a constitutive Trem2 knockout. Our study demonstrates that TREM2 regulates ST deficiency-induced neuroinflammation and astrocyte activation at the transcriptomic level but does not affect stage 1 disease-a

SUBMITTER: He S 

PROVIDER: S-EPMC12789058 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature