In this longitudinal study, emerging plasma biomarkers for neurodegenerative disease were compared between controls, patients with Alzheimer disease (AD), Lewy body dementia (LBD), frontotemporal dementia (FTD) and progressive supranuclear palsy (PSP). Findings demonstrate the role of plasma biomarkers in discriminating patients with different dementias, and at monitoring longitudinal alteration.

• A multicenter cohort of 300 participants (controls=73, amyloid positive mild cognitive impairment (MCI+) and AD dementia=63, LBD=117, FTD=28, PSP=19) was analyzed.

• In the MCI+AD group, increased p-tau181 (phosphorylated tau at threonine-181) was evident vs all other groups, and amyloid beta (Αβ)42/40 was lower in MCI+AD vs controls and FTD.

• Plasma biomarkers enabled classification between MCI+AD and controls, FTD and PSP with high precision but demonstrated limited ability in discriminating MCI+AD from LBD.

• P-tau181, neurofilament light (NfL) and glial fibrillar acidic protein (GFAP) were found to be linked with baseline and longitudinal cognitive decline in a disease specific pattern.

• Findings corroborated that p-tau181 was increased in MCI+AD, relative to controls, FTD and PSP, but was less accurate in the classification between MCI+AD and LBD or identifying amyloid brain pathology in LBD.

• All dementia groups exhibited elevated NfL, while MCI+AD and LBD had elevated GFAP.