PR001581 (Project)

Description:Frontotemporal dementia (FTD) lipidomic study of human brain from cases with GRN or C9orf72 mutations or controls. We aimed to determine how inherited mutations that cause FTD affect the brain lipidome. Both heterozygous GRN mutations and C9orf72 repeat expansions cause FTD with TDP-43 pathology, but GRN mutation carriers appear to have significant white matter pathology as seen by MRI. Our study uncovered significant loss of myelin sphingolipids in the heavily affected superior frontal white matter in both FTD groups, but GRN carriers show more severe myelin attrition than C9orf72 repeat expansion carriers. GRN carriers also showed selective increase in cholesterol esters and sphingosine in the less affected superior parietal white matter.