title: A Multiplex Protein Panel Applied to Cerebrospinal Fluid Reveals Three New Biomarker Candidates in ALS but None in Neuropathic Pain Patients.
abstract: The objective of this study was to develop and apply a novel multiplex panel of solid-phase proximity ligation assays (SP-PLA) requiring only 20 μL of samples, as a tool for discovering protein biomarkers for neurological disease and treatment thereof in cerebrospinal fluid (CSF). We applied the SP-PLA to samples from two sets of patients with poorly understood nervous system pathologies amyotrophic lateral sclerosis (ALS) and neuropathic pain, where patients were treated with spinal cord stimulation (SCS). Forty-seven inflammatory and neurotrophic proteins were measured in samples from 20 ALS patients and 15 neuropathic pain patients, and compared to normal concentrations in CSF from control individuals. Nineteen of the 47 proteins were detectable in more than 95% of the 72 controls. None of the 21 proteins detectable in CSF from neuropathic pain patients were significantly altered by SCS. The levels of the three proteins, follistatin, interleukin-1 alpha, and kallikrein-5 were all significantly reduced in the ALS group compared to age-matched controls. These results demonstrate the utility of purpose designed multiplex SP-PLA panels in CSF biomarker research for understanding neuropathological and neurotherapeutic mechanisms. The protein changes found in the CSF of ALS patients may be of diagnostic interest.
authors.affiliation: Department of Surgical Sciences, Anaesthesiology and Intensive Care and Uppsala Berzelii Technology Center for Neurodiagnostics, Uppsala University, Uppsala, Sweden.
authors.forename: Anne-Li
authors.initials: AL
authors.lastname: Lind
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Medical Sciences, Cancer Pharmacology and Computational Medicine, Science for Life Laboratory, Bioinformatics Infrastructure for Life Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Freyhult
authors.affiliation: Department of Anaesthesia and Intensive Care, University of Medicine and Pharmacy, Cluj, Napoca, Romania.
authors.forename: Constantin
authors.initials: C
authors.lastname: Bodolea
authors.affiliation: Department of Engineering Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Titti
authors.initials: T
authors.lastname: Ekegren
authors.affiliation: Department of Medical Sciences, Biochemical Structure and Function, Uppsala University, Uppsala, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Larsson
authors.affiliation: Department of Medical Sciences, Cancer Pharmacology and Computational Medicine, Uppsala University, Uppsala, Sweden.
authors.forename: Mats G
authors.initials: MG
authors.lastname: Gustafsson
authors.affiliation: Department of Surgical Sciences, Anaesthesiology and Intensive Care and Uppsala Berzelii Technology Center for Neurodiagnostics, Uppsala University, Uppsala, Sweden.
authors.forename: Lenka
authors.initials: L
authors.lastname: Katila
authors.affiliation: Department of Chemistry-BMC, Analytical Chemistry and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergquist
authors.affiliation: Department of Surgical Sciences, Anaesthesiology and Intensive Care and Uppsala Berzelii Technology Center for Neurodiagnostics, Uppsala University, Uppsala, Sweden.
authors.forename: Torsten
authors.initials: T
authors.lastname: Gordh
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Landegren
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Masood
authors.initials: M
authors.lastname: Kamali-Moghaddam
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D002556:Cerebrospinal Fluid Proteins / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009437:Neuralgia / Q000134:cerebrospinal fluid*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D002556:Cerebrospinal Fluid Proteins