Plasma proteome profiling identified biomarkers for the differential diagnosis and molecular staging of neurodegenerative dementias
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Plasma biomarkers are emerging as noninvasive tools to detect neurodegenerative diseases and monitor treatments in clinical trials. The bPRIDE study investigates blood-based biomarkers to improve the differential diagnosis and molecular staging of Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). Using proximity extension assay proteomics, we analyzed n=1319 plasma samples from 6 well-characterized cohorts. More than 200 proteins were found dysregulated across the different groups. Levels of GFAP showed the most substantial increase along AD clinical continuum. Levels of Integrin proteins ITGAV and ITGAM were the strongest downregulated proteins in Lewy body disorders and correlated with α-synuclein pathology in an independent autopsy-confirmed cohort (n=129). High NEFL and low GFAP levels were the strongest markers specifically associated to FTD. Findings were translated into a selection of 21 proteins to enable classification and staging models across different causes of dementia with high diagnostic performances within one single assay.
