Trajectories of CSF and plasma biomarkers across Alzheimer's disease continuum: disease staging by NF-L, p-tau181, and GFAP

CSF-to-plasma transition will open new avenues for molecular phenotyping of Alzheimer's disease (AD). Here we evaluated a panel of AD biomarkers in matched CSF and plasma samples across the AD continuum, from pre clinical AD to dementia. The aims were to: 1) compare diagnostic performance of the two biofluids, 2) evaluate trajectories of the biomarkers along AD progression. We analyzed CSF and plasma A1342/40, p-tau181, p-tau231, t-tau, NF-L, GFAP, UCHL-1 and CSF SNAP-25 in a cohort (n = 173) of preclinical AD, MCI-AD, AD dementia, frontotemporal dementia patients, and controls. We found a significant correlation between CSF and plasma levels of A1342/40, p-tau181, p-tau231, NF-L, and GFAP, while no CSF-plasma correlation was observed for t-tau and UCHL-1. Next to the core CSF biomarkers (A1342/40, p-tau181, t-tau), those providing the best discrimination between controls and preclinical AD were CSF p-tau231 and SNAP-25 and plasma A1342/40, p-tau231, and GFAP. Among plasma biomarkers, we found A1342/A1340, GFAP, and p-tau231 to show the largest rate of change at the CSF biomarker-defined cut-offs for amyloidosis and tauopathy. Finally, we identified GFAP, NF-L, and ptau181 as the biomarkers most significantly associated with disease progression in both CSF and plasma. We suggest that a well-standardized and validated panel of selected plasma markers can facilitate early AD diagnosis, even at the asymptomatic disease stage. We propose that both CSF and plasma measurement of NF-L, p-tau181, and GFAP may play a significant role in disease staging and monitoring.

Automated summary

The transition from cerebrospinal fluid (CSF) to plasma provides new avenues for studying molecular phenotypes of Alzheimer's disease (AD). This study evaluated a panel of AD biomarkers in matched CSF and plasma samples, comparing their diagnostic performance and evaluating their trajectories along the AD progression. The findings suggest that a standardized panel of selected plasma markers can facilitate early AD diagnosis and monitoring of disease progression.