A novel multi-marker discovery approach identifies new serum biomarkers for Parkinson’s disease in older people: an EXosomes in PArkiNson Disease (EXPAND) ancillary study

Calvani, Riccardo; Picca, Anna; Landi, Giovanni; Marini, Federico; Biancolillo, Alessandra; Coelho-Junior, Hélio José; Gervasoni, Jacopo; Persichilli, Silvia; Primiano, Aniello; Arcidiacono, Annalaura; Urbani, Andrea; Bossola, Maurizio; Bentivoglio, Anna Rita; Cesari, Matteo; Bernabei, Roberto; Monaco, Maria Rita Lo; Marzetti, Emanuele

doi:10.1007/s11357-020-00192-2

Original Article
Published: 26 May 2020

A novel multi-marker discovery approach identifies new serum biomarkers for Parkinson’s disease in older people: an EXosomes in PArkiNson Disease (EXPAND) ancillary study

GeroScience volume 42, pages 1323–1334 (2020)Cite this article

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Abstract

Dopaminergic nigrostriatal denervation and widespread intracellular α-synuclein accumulation are neuropathologic hallmarks of Parkinson’s disease (PD). A constellation of peripheral processes, including metabolic and inflammatory changes, are thought to contribute to neurodegeneration. In the present study, we sought to obtain insight into the multifaceted pathophysiology of PD through the application of a multi-marker discovery approach. Fifty older adults aged 70+, 20 with PD and 30 age-matched controls were enrolled as part of the EXosomes in PArkiNson Disease (EXPAND) study. A panel of 68 circulating mediators of inflammation, neurogenesis and neural plasticity, and amino acid metabolism was assayed. Biomarker selection was accomplished through sequential and orthogonalized covariance selection (SO-CovSel), a multi-platform regression method developed to handle highly correlated variables organized in multi-block datasets. The SO-CovSel model with the best prediction ability using the smallest number of variables was built with seven biomolecules. The model allowed correct classification of 94.2 ± 3.1% participants with PD and 100% controls. The biomarker profile of older adults with PD was defined by higher circulating levels of interleukin (IL) 8, macrophage inflammatory protein (MIP)-1β, phosphoethanolamine, and proline, and by lower concentrations of citrulline, IL9, and MIP-1α. Our innovative approach allowed identifying and evaluating the classification performance of a set of potential biomarkers for PD in older adults. Future studies are warranted to establish whether these biomolecules could serve as biomarkers for PD as well as unveil new targets for interventions.

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Data availability

Data analyzed in the current study are available from the corresponding author upon reasonable request.

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Funding

This work was supported by Innovative Medicine Initiative-Joint Undertaking (IMI-JU no. 115621), the non-profit research foundation “Centro Studi Achille e Linda Lorenzon,” and by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES; Finance Code 001).

Author information

Riccardo Calvani and Anna Picca contributed equally to this work.

Affiliations

Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, Rome, Italy
Riccardo Calvani, Anna Picca, Giovanni Landi, Jacopo Gervasoni, Silvia Persichilli, Annalaura Arcidiacono, Andrea Urbani, Maurizio Bossola, Anna Rita Bentivoglio, Roberto Bernabei, Maria Rita Lo Monaco & Emanuele Marzetti
Department of Chemistry, Sapienza Università di Roma, Rome, Italy
Federico Marini & Alessandra Biancolillo
Department of Physical and Chemical Sciences, Università degli Studi dell’Aquila, L’Aquila, Italy
Alessandra Biancolillo
Università Cattolica del Sacro Cuore, Rome, Italy
Hélio José Coelho-Junior, Jacopo Gervasoni, Silvia Persichilli, Aniello Primiano, Andrea Urbani, Maurizio Bossola, Anna Rita Bentivoglio, Roberto Bernabei & Emanuele Marzetti
Applied Kinesiology Laboratory–LCA, School of Physical Education, Universidade Estadual de Campinas, Campinas, SP, Brazil
Hélio José Coelho-Junior
Department of Clinical Sciences and Community Health, Università di Milano, Milan, Italy
Matteo Cesari
Geriatric Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
Matteo Cesari

Authors

Riccardo Calvani
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Anna Picca
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Giovanni Landi
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Federico Marini
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Alessandra Biancolillo
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Hélio José Coelho-Junior
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Jacopo Gervasoni
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Silvia Persichilli
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Aniello Primiano
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Annalaura Arcidiacono
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Andrea Urbani
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Maurizio Bossola
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Anna Rita Bentivoglio
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Matteo Cesari
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Roberto Bernabei
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Maria Rita Lo Monaco
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Emanuele Marzetti
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Contributions

A.P. and R.C. conceived and developed the study. A.R.B., H.J.C.-J., G.L., and M.R.L.M. coordinated participant recruitment and assessment. A.A., J.G., S.P., and A.Pr. developed and conducted metabolomics analysis. M.B. and A.P. performed immunoassays for cytokine quantification. A.B. and F.M. developed and packaged MATLAB scripts for the SO-CovSel algorithm. R.B., M.C., E.M., and A.U. contributed critical input towards study design and manuscript development. All authors edited and approved the final version of the manuscript.

Corresponding authors

Correspondence to Anna Picca or Maria Rita Lo Monaco.

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The study was conducted in agreement with legal requirements and international norms (Declaration of Helsinki 1964). The study protocol was approved by the Ethics Committee of the Università Cattolica del Sacro Cuore, Rome, Italy (protocol no. 0045298/17).

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Calvani, R., Picca, A., Landi, G. et al. A novel multi-marker discovery approach identifies new serum biomarkers for Parkinson’s disease in older people: an EXosomes in PArkiNson Disease (EXPAND) ancillary study. GeroScience 42, 1323–1334 (2020). https://doi.org/10.1007/s11357-020-00192-2

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Received: 07 January 2020
Accepted: 16 April 2020
Published: 26 May 2020
Issue Date: October 2020
DOI: https://doi.org/10.1007/s11357-020-00192-2

Keywords

Metabolomics
Amino acids
Cytokines
Neurodegeneration
Aging
Personalized medicine