Verification of a Parkinson's disease protein signature in T-lymphocytes by multiple reaction monitoring.

Tiziana Alberio, Kelly Mc Mahon, Manuela Cuccurullo, Lee Gethings, Craig Lawless, Maurizio Zibetti, Leonardo Lopiano, Johannes Vissers, Mauro Fasano

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Diagnosis of Parkinson’s disease, the second most common neurodegenerative disease, is based on the appearance of motor symptoms. A panel of protein biomarkers in the T-lymphocyte proteome was previously proposed as a Parkinson’s disease signature. Here, we designed an LC–MS based method to quantitatively evaluate this protein signature by multiple reaction monitoring (MRM) in T-lymphocytes and peripheral blood mononuclear cells from a new cohort of nine patients with Parkinson’s disease and nine unaffected subjects. Patients were classified using the discriminant function obtained from two-dimensional electrophoresis and protein amounts measured by MRM, thus assigning seven controls out of nine as true negatives and nine patients out of nine as true positives. A good discriminant power was obtained by selecting a subset of peptides from the protein signature, with an area under the receiver operating characteristic curve of 0.877. A similar result is achieved by evaluating all peptides of a selected panel of proteins (gelsolin, moesin, septin-6, twinfilin-2, lymphocyte-specific protein 1, vimentin, transaldolase), with an area under the curve of 0.840. Conversely, the signature was not able to classify the enrolled subjects when evaluated in whole mononuclear cells. Overall, this report shows the portability of the proposed method to a large-scale clinical validation study.

    Keywords: biomarkers; multiple reaction monitoring; Parkinson’s disease; peripheral blood lymphocytes
    Original languageEnglish
    Pages (from-to)3554–3561
    Number of pages8
    JournalJournal of Proteome Research
    Volume13
    Issue number8
    DOIs
    Publication statusPublished - Jun 2014

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