Reduced plasma hexosylceramides in frontotemporal dementia are a biomarker of white matter integrity
Oana C. Marian, Sophie Matis, Carol Dobson‐Stone, Woojin S. Kim, John B. Kwok, Olivier Piguet, Glenda M. Halliday, Ramon Landin‐Romero, Anthony S. DonAbstract
INTRODUCTION
Blood biomarkers are needed to facilitate new therapeutic trials and improve management of behavioral 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.
METHODS
Nineteen glycolipids were quantified in bvFTD (n = 31) and control (n = 26) plasma samples. White matter integrity was assessed using magnetic resonance imaging (MRI)‐derived fiber tract density and cross‐section (FDC).
RESULTS
Eleven lipids were significantly lower in bvFTD compared to control subjects, and seven were inversely correlated with disease duration, 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 of these tracts in bvFTD but not control subjects.
DISCUSSION
Circulating glycolipids may be a valuable biomarker of myelin integrity and disease progression in FTD.
Highlights
Blood biomarkers are needed for behavioral variant frontotemporal dementia (bvFTD). Plasma hexosylceramides are reduced in bvFTD cases compared with normal controls. Plasma hexosylceramides correlate with disease duration in bvFTD. Plasma hexosylceramides correlate with brain white matter integrity in bvFTD. Plasma glycolipids have potential as biomarkers of disease progression in bvFTD.