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.
Highlights
Many neurological conditions would benefit from molecular biomarkers for improved understanding of diseases and their susceptibility to treatment
Follistatin, interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta) and kallikrein-5 (KLK5), were found at significantly lower levels in the amyotrophic lateral sclerosis (ALS) samples than in control samples (p
We report decreased levels of follistatin, IL-1 alpha and KLK5 in cerebrospinal fluid (CSF) from ALS patients compared to controls
Summary
Many neurological conditions would benefit from molecular biomarkers for improved understanding of diseases and their susceptibility to treatment. The solid phase proximity ligation assay (SP-PLA) [2] and other high-performance DNA-assisted proximity assays [3, 4], meet these requirements [5,6,7] by using pairs or trios of antibodies with attached oligonucleotides. These technologies have identified biomarker candidates for cardiovascular diseases [6] and cancers [4, 8] using only 1–5 μL samples of blood plasma. A panel that includes inflammatory, glial, and neurotrophic proteins may be relevant for discovery stage investigations in several, if not most, diseases and treatments of the nervous system
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