Altered myelin sphingolipid and glycerophospholipid profiles in Huntington disease.

Authors

Michael G Friedrich, Gabrielle R Phillips, Reuben Se Young, Sarah Cameron, Luke K Bale, Jesse A Michael, Huaqi Su, Helena Targa Dias Anastacio, Catriona A McLean, Gavin E Reid, Todd W Mitchell

Published in

Journal of Huntington's disease. Pages 18796397261472539. Aug 04, 2026. Epub Aug 04, 2026.

Abstract

Huntington's disease (HD) is a fatal neurodegenerative disease caused by a CAG repeat expansion in the Huntingtin gene (HTT). While classically considered a disease of grey matter, recent imaging data have revealed presymptomatic abnormalities in white matter (WM) tracts. Here, we report lipid changes in glycerophospholipids and sphingolipids from enriched myelin extracts of three WM tracts (internal capsule (IC), dorsomedial prefrontal cortex (dmPFC), corpus callosum (CC)) of HD and control donors. We found no difference in total lipid concentration between HD and control myelin. However, changes were observed at the lipid class level for the CC and dmPFC, with a reduction in the proportion of Hexosylceramides in HD myelin. When lipids were examined at a species level, there was a shift towards shorter glycerophospholipid fatty acid chain length in HD for all three regions, most notably in phosphatidylethanolamine species. This coincides with previous data showing a reduction in fatty acyl chain lengths in sphingolipid species in the caudate of the same donor cohort and suggests a widespread impact of HD on fatty acid metabolism in the brain.

PMID:
42550884
Bibliographic data and abstract were imported from PubMed on 05 Aug 2026.

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