Systematic Assessment of 10 Biomarker Candidates Focusing on α‐Synuclein‐Related Disorders

ABSTRACT Background Objective diagnostic biomarkers are needed to support a clinical diagnosis. Objectives To analyze markers in various neurodegenerative disorders to identify diagnostic biomarker candidates for mainly α‐synuclein (aSyn)‐related disorders (ASRD) in serum and/or cerebrospinal fluid (CSF). Methods Upon initial testing of commercially available kits or published protocols for the quantification of the candidate markers, assays for the following were selected: total and phosphorylated aSyn (pS129aSyn), neurofilament light chain (NfL), phosphorylated neurofilament heavy chain (pNfH), tau protein (tau), ubiquitin C‐terminal hydrolase L1 (UCHL‐1), glial fibrillary acidic protein (GFAP), calcium‐binding protein B (S100B), soluble triggering receptor expressed on myeloid cells 2 (sTREM‐2), and chitinase‐3‐like protein 1 (YKL‐40). The cohort comprised participants with Parkinson's disease (PD, n = 151), multiple system atrophy (MSA, n = 17), dementia with Lewy bodies (DLB, n = 45), tau protein‐related neurodegenerative disorders (n = 80, comprising patients with progressive supranuclear palsy (PSP, n = 38), corticobasal syndrome (CBS, n = 16), Alzheimer's disease (AD, n = 11), and frontotemporal degeneration/amyotrophic lateral sclerosis (FTD/ALS, n = 15), as well as healthy controls (HC, n = 20). Receiver operating curves (ROC) with area under the curves (AUC) are given for each marker. Results CSF total aSyn was decreased. NfL, pNfH, UCHL‐1, GFAP, S100B, and sTREM‐2 were increased in patients with neurodegenerative disease versus HC (P