Amyotrophic lateral sclerosis multiprotein biomarkers in peripheral blood mononuclear cells

Giovanni Nardo, Silvia Pozzi, Mauro Pignataro, Eliana Lauranzano, Giorgia Spano, Silvia Garbelli, Stefania Mantovani, Kalliopi Marinou, Laura Papetti, Marta Monteforte, Valter Torri, Luca Paris, Gianfranco Bazzoni, Christian Lunetta, Massimo Corbo, Gabriele Mora, Caterina Bendotti, Valentina Bonetto

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Amyotrophic lateral sclerosis (ALS) is a fatal progressive motor neuron disease, for which there are still no diagnostic/prognostic test and therapy. Specific molecular biomarkers are urgently needed to facilitate clinical studies and speed up the development of effective treatments. Methodology/Principal Findings: We used a two-dimensional difference in gel electrophoresis approach to identify in easily accessible clinical samples, peripheral blood mononuclear cells (PBMC), a panel of protein biomarkers that are closely associated with ALS. Validations and a longitudinal study were performed by immunoassays on a selected number of proteins. The same proteins were also measured in PBMC and spinal cord of a G93A SOD1 transgenic rat model. We identified combinations of protein biomarkers that can distinguish, with high discriminatory power, ALS patients from healthy controls (98%), and from patients with neurological disorders that may resemble ALS (91%), between two levels of disease severity (90%), and a number of translational biomarkers, that link responses between human and animal model. We demonstrated that TDP-43, cyclophilin A and ERp57 associate with disease progression in a longitudinal study. Moreover, the protein profile changes detected in peripheral blood mononuclear cells of ALS patients are suggestive of possible intracellular pathogenic mechanisms such as endoplasmic reticulum stress, nitrative stress, disturbances in redox regulation and RNA processing. Conclusions/Significance: Our results indicate that PBMC multiprotein biomarkers could contribute to determine amyotrophic lateral sclerosis diagnosis, differential diagnosis, disease severity and progression, and may help to elucidate pathogenic mechanisms.

Original languageEnglish
Article numbere25545
JournalPLoS One
Volume6
Issue number10
DOIs
Publication statusPublished - Oct 5 2011

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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