Cognitive and functional performance and plasma biomarkers of early Alzheimer's disease in Down syndrome

INTRODUCTIONPeople with Down syndrome (DS) have a 75% to 90% lifetime risk of Alzheimer's disease (AD). AD pathology begins a decade or more prior to onset of clinical AD dementia in people with DS. It is not clear if plasma biomarkers of AD pathology are correlated with early cognitive and functional impairments in DS, and if these biomarkers could be used to track the early stages of AD in DS or to inform inclusion criteria for clinical AD treatment trials.METHODSThis large cross-sectional cohort study investigated the associations between plasma biomarkers of amyloid beta (A beta)42/40, total tau, and neurofilament light chain (NfL) and cognitive (episodic memory, visual-motor integration, and visuospatial abilities) and functional (adaptive behavior) impairments in 260 adults with DS without dementia (aged 25-81 years).RESULTSIn general linear models lower plasma A beta 42/40 was related to lower visuospatial ability, higher total tau was related to lower episodic memory, and higher NfL was related to lower visuospatial ability and lower episodic memory.DISCUSSIONPlasma biomarkers may have utility in tracking AD pathology associated with early stages of cognitive decline in adults with DS, although associations were modest.Highlights Plasma Alzheimer's disease (AD) biomarkers correlate with cognition prior to dementia in Down syndrome. Lower plasma amyloid beta 42/40 was related to lower visuospatial abilities. Higher plasma total tau and neurofilament light chain were associated with lower cognitive performance. Plasma biomarkers show potential for tracking early stages of AD symptomology.