Cullen, Nicholas C.Leuzy, AntoineJanelidze, ShorenaPalmqvist, SebastianSvenningsson, Anna L.Stomrud, ErikDage, Jeffrey L.Mattsson-Carlgren, NiklasHansson, Oskar2025-03-102025-03-102021-06-11Cullen NC, Leuzy A, Janelidze S, et al. Plasma biomarkers of Alzheimer's disease improve prediction of cognitive decline in cognitively unimpaired elderly populations. Nat Commun. 2021;12(1):3555. Published 2021 Jun 11. doi:10.1038/s41467-021-23746-0https://hdl.handle.net/1805/46274Plasma biomarkers of amyloid, tau, and neurodegeneration (ATN) need to be characterized in cognitively unimpaired (CU) elderly individuals. We therefore tested if plasma measurements of amyloid-β (Aβ)42/40, phospho-tau217 (P-tau217), and neurofilament light (NfL) together predict clinical deterioration in 435 CU individuals followed for an average of 4.8 ± 1.7 years in the BioFINDER study. A combination of all three plasma biomarkers and basic demographics best predicted change in cognition (Pre-Alzheimer's Clinical Composite; R2 = 0.14, 95% CI [0.12-0.17]; P < 0.0001) and subsequent AD dementia (AUC = 0.82, 95% CI [0.77-0.91], P < 0.0001). In a simulated clinical trial, a screening algorithm combining all three plasma biomarkers would reduce the required sample size by 70% (95% CI [54-81]; P < 0.001) with cognition as trial endpoint, and by 63% (95% CI [53-70], P < 0.001) with subsequent AD dementia as trial endpoint. Plasma ATN biomarkers show usefulness in cognitively unimpaired populations and could make large clinical trials more feasible and cost-effective.en-USAttribution 4.0 InternationalAlzheimer's diseaseNeurodegenerationPredictive markersArticle