Targeted Multiple Reaction Monitoring Analysis of CSF Identifies UCHL1 and GPNMB as Candidate Biomarkers for ALS

• DOI: 10.1007/s12031-019-01411-y
• Publication Date: 2019-11-12T19:03:03Z
• Authors: Shaochun Zhu; Anna Wuolikainen; Junfang Wu; Anders Öhman; Gunnar Wingsle; Thomas Moritz; Peter M. Andersen; Lars Forsgren; Miles Trupp
• Keywords: Proteomics; Adult; Male; Neurologi; Parkinson's disease; CSF biomarker; Article; Mass Spectrometry; 03 medical and health sciences; 0302 clinical medicine; Humans; Aged; Membrane Glycoproteins; Amyotrophic Lateral Sclerosis; Neurosciences; Middle Aged; Survival Analysis; Neurology; Molecular Diagnostic Techniques; Female; ALS; Protein homeostasis; Ubiquitin Thiolesterase; Neurovetenskaper; Biomarkers

Abstract The neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD) share some common molecular deficits including disruption of protein homeostasis leading to disease-specific aggregation. While insoluble aggregates are the defining pathological confirmation diagnosis, patient stratification based on early etiologies may identify distinct subgroups within a clinical diagnosis that would respond differently in therapeutic development programs. We developing targeted multiple reaction monitoring (MRM) mass spectrometry methods rigorously quantify CSF proteins from known genes involved lysosomal, ubiquitin-proteasomal, autophagy pathways. Analysis 21 PD, ALS, 25 control patients, matched for gender, age, age sample, revealed significant changes peptide levels between control. In patients with two peptides chromogranin B (CHGB, secretogranin 1) were significantly reduced. ubiquitin carboxy-terminal hydrolase like 1 (UCHL1) one each glycoprotein non-metastatic melanoma (GPNMB) cathepsin D (CTSD) all increased. ALS separated into groups length survival after sampling increases GPNMB UCHL1 specific short-lived patients. analysis additional cohorts is required validate these candidate biomarkers, this study suggests trials identifies targets drug efficacy measurements during development.