BACE-1, PS-1 and sAPPβ Levels Are Increased in Plasma from Sporadic Inclusion Body Myositis Patients: Surrogate Biomarkers among Inflammatory Myopathies

• Published in: Molecular medicine (Cambridge, Mass.) Vol. 21; no. 1; pp. 817 - 823
• Main Authors: Catalán-García, Marc, Garrabou, Glòria, Morén, Constanza, Guitart-Mampel, Mariona, Gonzalez-Casacuberta, Ingrid, Hernando, Adriana, Gallego-Escuredo, Jose Miquel, Yubero, Dèlia, Villarroya, Francesc, Montero, Raquel, O-Callaghan, Albert Selva, Cardellach, Francesc, Grau, Josep Maria
• Format: Journal Article
• Language: English
• Published: England BioMed Central 01.03.2016; The Feinstein Institute Press
• Subjects: Alzheimer's disease; Biomarkers; Biopsy; Enzymes; Hospitals; Inflammation; Inflammatory diseases; Mitochondrial DNA; Musculoskeletal diseases; Peptides; Plasma; Proteins; Tumor necrosis factor-TNF; Spain
• ISSN: 1076-1551; 1528-3658
• DOI: 10.2119/molmed.2015.00168

Sporadic inclusion body myositis (sIBM) is a rare disease that is difficult to diagnose. Muscle biopsy provides three prominent pathological findings: inflammation, mitochondrial abnormalities and fibber degeneration, represented by the accumulation of protein depots constituted by β-amyloid peptide, among others. We aim to perform a screening in plasma of circulating molecules related to the putative etiopathogenesis of sIBM to determine potential surrogate biomarkers for diagnosis. Plasma from 21 sIBM patients and 20 age- and gender-paired healthy controls were collected and stored at -80°C. An additional population of patients with non-sIBM inflammatory myopathies was also included (nine patients with dermatomyositis and five with polymyositis). Circulating levels of inflammatory cytokines (interleukin [IL]-6 and tumor necrosis factor [TNF]-α), mitochondrial-related molecules (free plasmatic mitochondrial DNA [mtDNA], fibroblast growth factor-21 [FGF-21] and coenzyme-Q10 [CoQ]) and amyloidogenic-related molecules (beta-secretase-1 [BACE-1], presenilin-1 [PS-1], and soluble Aβ precursor protein [sAPPβ]) were assessed with magnetic bead-based assays, real-time polymerase chain reaction, enzyme-linked immunosorbent assay (ELISA) and high-pressure liquid chromatography (HPLC). Despite remarkable trends toward altered plasmatic expression of inflammatory and mitochondrial molecules (increased IL-6, TNF-α, circulating mtDNA and FGF-21 levels and decreased content in CoQ), only amyloidogenic degenerative markers including BACE-1, PS-1 and sAPPβ levels were significantly increased in plasma from sIBM patients compared with controls and other patients with non-sIBM inflammatory myopathies ( < 0.05). Inflammatory, mitochondrial and amyloidogenic degeneration markers are altered in plasma of sIBM patients confirming their etiopathological implication in the disease. Sensitivity and specificity analysis show that BACE-1, PS-1 and sAPPβ represent a good predictive noninvasive tool for the diagnosis of sIBM, especially in distinguishing this disease from polymyositis.