Molecular Medicine

, Volume 21, Issue 1, pp 817–823 | Cite as

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

  • Marc Catalán-García
  • Glòria Garrabou
  • Constanza Morén
  • Mariona Guitart-Mampel
  • Ingrid Gonzalez-Casacuberta
  • Adriana Hernando
  • Jose Miquel Gallego-Escuredo
  • Dèlia Yubero
  • Francesc Villarroya
  • Raquel Montero
  • Albert Selva O-Callaghan
  • Francesc Cardellach
  • Josep Maria Grau
Research Article


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 (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 noninvasive tool for the diagnosis of sIBM, especially in distinguishing this disease from polymyositis.



This study has been funded by Fondo de Investigación Sanitaria (FIS 0229/08, 00462/11 and 01199/12) granted by ISCIII and Fondo Europeo de Desarrollo Regional (FEDER), Fundació Cellex, Fundación para la Investigación y la Prevención del SIDA en España (FIPSE 360745/09 and 360982/10), Suports a Grups de Recerca de la Generalitat de Catalunya (SGR 09/1158 and 09/1385) and CIBER de Enfermedades Raras (CIBERER, an initiative of ISCIII).


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Authors and Affiliations

  • Marc Catalán-García
    • 1
  • Glòria Garrabou
    • 1
  • Constanza Morén
    • 1
  • Mariona Guitart-Mampel
    • 1
  • Ingrid Gonzalez-Casacuberta
    • 1
  • Adriana Hernando
    • 1
  • Jose Miquel Gallego-Escuredo
    • 2
  • Dèlia Yubero
    • 3
    • 4
  • Francesc Villarroya
    • 2
  • Raquel Montero
    • 3
    • 4
  • Albert Selva O-Callaghan
    • 5
  • Francesc Cardellach
    • 1
  • Josep Maria Grau
    • 1
  1. 1.Laboratory of Muscle Research and Mitochondrial Function, Cellex-IDIBAPS, Faculty of Medicine, Department of Internal Medicine, Hospital Clinic of BarcelonaUniversity of BarcelonaBarcelonaSpain
  2. 2.Department of Biochemistry and Molecular BiologyInstitute of Biomedicine (University of Barcelona), University of Barcelona, and CIBEROBNBarcelonaSpain
  3. 3.Clinical Biochemistry DepartmentHospital Sant Joan de DéuBarcelonaSpain
  4. 4.CIBERERValenciaSpain
  5. 5.Internal Medicine DepartmentHospital Vall d’HebronBarcelonaSpain

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