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bioRxiv · 10.1101/2025.02.17.638741

Reduced plasma hexosylceramides in frontotemporal dementia are a biomarker of white matter integrity

Marian, O. C.·Matis, S.·Dobson-Stone, C.·Kim, W. S.·Kwok, J. B.·Piguet, O.·Halliday, G. M.·Landin-Romero, R.·Don, A. S.
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Abstract

INTRODUCTIONBlood biomarkers are needed to facilitate new therapeutic trials and improve management of behavioural variant frontotemporal dementia (bvFTD). Since altered white matter integrity is characteristic of bvFTD, this study aimed to determine if plasma levels of myelin-enriched glycolipids are altered in bvFTD and correlate with white matter integrity. METHODSNineteen glycolipids were quantified in bvFTD (n=31) and control (n=26) plasma samples. White matter integrity was assessed using MRI-derived fibre tract density and cross-section (FDC). RESULTSEleven lipids were significantly lower in bvFTD compared to control subjects, seven were inversely correlated with disease duration, and twelve were positively correlated with cognitive performance, with C22:0 hexosylceramide most strongly correlated. FDC was lower in frontotemporal white matter tracts of bvFTD compared to control subjects, and plasma C22:0 hexosylceramide was significantly correlated with FDC in these tracts. DISCUSSIONCirculating glycolipids may be a valuable biomarker of myelin integrity and disease progression in FTD.

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Marian, O. C., Matis, S., Dobson-Stone, C., Kim, W. S., Kwok, J. B., Piguet, O., Halliday, G. M., Landin-Romero, R., Don, A. S.. 2025-02-23. Reduced plasma hexosylceramides in frontotemporal dementia are a biomarker of white matter integrity. https://doi.org/10.1101/2025.02.17.638741

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