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BACE-1, PS-1 and sAPPβ levels are increased in plasma from sporadic inclusion body myositis patients: surrogate biomarkers among inflammatory myopathies
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Sporadic inclusion body myositis (sIBM) is a rare disease which 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 -80ºC. An additional population of patients with non-sIBM inflammatory myopathies was also included (9 patients with dermatomyositis and 5 with polymyositis). Circulating levels of inflammatory cytokines (IL-6 and TNF-α), mitochondrial-related molecules (free plasmatic mtDNA, FGF-21 and CoQ) and amyloidogenic-related molecules (BACE-1, PS-1 and sAPPβ) were assessed with magnetic bead-based assays, rt-PCR, ELISA and HPLC. Despite remarkable trends towards 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 to controls and other patients with non-sIBM inflammatory myopathies (p<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 non-invasive tool for the diagnosis of sIBM, especially in distinguishing this disease from polymyositis.
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VILLARROYA I GOMBAU, Francesc, CATALÁN GARCÍA, Marc, GARRABOU TORNOS, Glòria, MORÉN NÚÑEZ, Constanza, GUITART MAMPEL, Mariona, GONZÁLEZ CASACUBERTA, Ingrid, HERNANDO, Adriana, GALLEGO ESCUREDO, José miguel, YUBERO SILES, Dèlia, MONTERO, Raquel, SELVA O'CALLAGHAN, Albert, CARDELLACH, Francesc, GRAU, Josep maria. BACE-1, PS-1 and sAPPβ levels are increased in plasma from sporadic inclusion body myositis patients: surrogate biomarkers among inflammatory myopathies. _Molecular Medicine_. 2015. Vol. 21, núm. 1, pàgs. 817-823. [consulta: 25 de gener de 2026]. ISSN: 1076-1551. [Disponible a: https://hdl.handle.net/2445/219049]