Association of plasma neurofilament light chain with microstructural white matter changes in Down syndrome

INTRODUCTIONBoth micro- and macrostructural white matter (WM) abnormalities, particularly those related to axonal degeneration, are associated with cognitive decline in adults with Down syndrome (DS) prior to a diagnosis of Alzheimer disease. Neurofilament light chain (NfL) is a support protein within myelinated axons released into blood following axonal damage. In this study we investigated cross-sectional relationships between WM microstructural changes as measured by diffusion tensor imaging (DTI) and plasma NfL concentration in adults with DS without dementia.METHODSThirty cognitively stable (CS) adults with DS underwent diffusion-weighted MRI scanning and plasma NfL measurement. DTI measures of select WM tracts were derived using automatic fiber tracking, and associations with plasma NfL were assessed using Spearman correlation coefficients.RESULTSHigher Plasma NfL was associated with greater altered diffusion measures of select tracts.DISCUSSIONEarly increases in plasma NfL may reflect early white matter microstructural changes prior to dementia in DS.Highlights The onset of such WM changes in DS has not yet been widely studied. WM microstructural properties correlated with plasma neurofilament light chain (NfL). NfL may reflect early, selective WM changes in adults with DS at high risk of developing AD.