期刊
NEUROBIOLOGY OF DISEASE
卷 189, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2023.106356
关键词
Alzheimer's disease; preclinical Alzheimer's disease; Frontotemporal dementia; Biomarkers; Cerebrospinal fluid; Blood; Simoa
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.
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.
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