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 < 0.05). As expected, some of the markers were highest in AD (i.e., UCHL-1, GFAP, S100B, sTREM-2, YKL-40). Within ASRD, CSF NfL levels were higher in MSA than PD and DLB (P < 0.05). Comparing PD to HC, interesting serum markers were S100B (AUC: 0.86), sTREM2 (AUC: 0.87), and NfL (AUC: 0.78). CSF S100B and serum GFAP were highest in DLB.

CONCLUSIONS:

Levels of most marker candidates tested in serum and CSF significantly differed between disease groups and HC. In the stratification of PD versus other tau- or aSyn-related conditions, CSF NfL levels best discriminated PD and MSA. CSF S100B and serum GFAP best discriminated PD and DLB. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

• Authors: Isabel Schulz, Niels Kruse, Roland G Gera, Thomas Kremer, Jesse Cedarbaum, Robin Barbour, Wagner Zago, Sebastian Schade, Birgit Otte, Michael Bartl, Samantha J Hutten, Claudia Trenkwalder, Brit Mollenhauer
• Journal: Movement disorders : official journal of the Movement Disorder Society (Mov Disord) Vol. 36 Issue 12 Pg. 2874-2887 (12 2021) ISSN: 1531-8257 [Electronic] United States
• PMID: 34363416 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

Chemical References

• Biomarkers
• alpha-Synuclein
• tau Proteins

Topics

• Amyotrophic Lateral Sclerosis
• Biomarkers (cerebrospinal fluid)
• Frontotemporal Dementia
• Humans
• Multiple System Atrophy (diagnosis)
• alpha-Synuclein (cerebrospinal fluid)
• tau Proteins (cerebrospinal fluid)