The link between plasma and cognitive markers for Alzheimer's disease in Down syndrome: a longitudinal study.

BACKGROUND: Given the need to clarify the relationship between biomarkers, cognitive performance, and clinical status in Down syndrome (DS), this longitudinal study examined the influence of baseline clinical diagnosis on the evolution of plasma neurofilament light (NfL) and p-tau217, as well as the predictive value of baseline cognitive performance on biomarker trajectories and clinical conversion within the Alzheimer's disease (AD) continuum. METHODS: 57 adults with DS were classified as asymptomatic (ADS; n = 25), prodromal (PDS; n = 16), or dementia (DDS; n = 16). Clinical, neuropsychological, and biomarker assessments were conducted at baseline and after a 24-month follow-up. RESULTS: Biomarker levels increased significantly over time in pathological groups only, with the greatest increase observed in the DDS group. Baseline performance on the New Serial Learning Immediate test (NSLI) was the strongest predictor of biomarker evolution. Each one-point increase in baseline NSLI score was associated with a reduction of 0.035 units in the longitudinal increase of p-tau217 and 0.463 units in NfL. Baseline p-tau217 values were the only significant predictor of clinical conversion: individuals with values one unit above the sample median showed a 3.56-fold increased risk of progression to a more advanced clinical stage. CONCLUSION: These findings highlight the relevance of episodic memory performance as a predictor of biomarker progression, particularly p-tau217, and support its close association with clinical status and disease progression. The results support the development of screening strategies to identify DS individuals at high risk of rapid cognitive decline and to inform future therapeutic trials.