Plasma profiling reveals three proteins associated to amyotrophic lateral sclerosis

Abstract

ObjectiveAmyotrophic lateral sclerosis (ALS) is the most common adult motor neuron disease leading to muscular paralysis and death within 3–5 years from onset. Currently, there are no reliable and sensitive markers able to substantially shorten the diagnosis delay. The objective of the study was to analyze a large number of proteins in plasma from patients with various clinical phenotypes of ALS in search for novel proteins or protein profiles that could serve as potential indicators of disease.MethodsAffinity proteomics in the form of antibody suspension bead arrays were applied to profile plasma samples from 367 ALS patients and 101 controls. The plasma protein content was directly labeled and protein profiles obtained using 352 antibodies from the Human Protein Atlas targeting 278 proteins. A focused bead array was then built to further profile eight selected protein targets in all available samples.ResultsDisease-associated significant differences were observed and replicated for profiles from antibodies targeting the proteins: neurofilament medium polypeptide (NEFM), solute carrier family 25 (SLC25A20), and regulator of G-protein signaling 18 (RGS18).InterpretationUpon further validation in several independent cohorts with inclusion of a broad range of other neurological disorders as controls, the alterations of these three protein profiles in plasma could potentially provide new molecular markers of disease that contribute to the quest of understanding ALS pathology.

Proteins that mediate protein aggregation and cytotoxicity distinguish Alzheimer's hippocampus from normal controls

“…Aspartate aminotransferase and aldolase are major targets for deglycation repair by DJ‐1, which is highly induced in many cases of PD (Richarme et al ., 2015). Neurofilament medium polypeptide is one of three plasma proteins strongly associated with ALS (Haggmark et al ., 2014). Cytochrome c oxidase mutations and polymorphisms are associated with multiple neurodegenerative diseases, including AD (Loera‐Castaneda et al ., 2014).…”

Neuroproteomic profiling of human body fluids

“…[140]. As one example, light, medium, and heavy chains of neurofilaments have been reported as increased in CSF from MS, ALS, and AD patients, also with concordant levels in serum [31,32,111,141]. Also other common disease markers have been suggested within several neurodegenerative disorders as reviewed by Kroksveen et al [142].…”

“…So far, corresponding reports based on plasma analysis have been limited. We addressed this by an extensive plasma profiling study where we identified three proteins, namely neurofilament medium polypeptide (NEFM), regulator of G-protein signaling 18 (RGS18), and mitochondrial carnitine/acylcarnitine carrier protein (SLC25A20) as elevated in plasma from ALS patients [111].…”

The potential clinical impact of the tissue-based map of the human proteome

“…Tissue-elevated proteins could also be searched for and analyzed in serum, for example, using affinity proteomics on suspension bead arrays, as they represent an interesting group of proteins that may be suitable for serumbased diagnostic tests. In a recent study by Haggmark et al [7] focusing on plasma profiling in samples from amyotrophic lateral sclerosis, two out of the three proteins shown to be associated with the disease were tissue-elevated. Serum-based analysis can also be used to discover autoantigens for identification of potential autoimmune targets [8].…”