Poster Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

A different perspective of circulatory biomarker discovery in neurodegenerative diseases: combined use of alternative proteomics analyses to create a comprehensive “proteomics signature of the blood” (#411)

Sandra I. Anjo 1 2 , Rafael Silva 1 , Miguel Rosado 1 3 , Inês Baldeiras 1 2 4 , Alexandre Mendonça 5 , Cristina Januário 4 , Isabel Santana 1 2 4 , Ana Verdelho 5 6 , Diana Santos 7 , Andreia Gomes 7 , Miguel Castelo-Branco 7 , Bruno Manadas 1
  1. Center for Neuroscience and Cell Biology – University of Coimbra (CNC-UC), Coimbra, PORTUGAL, Portugal
  2. Faculty of Medicine, University of Coimbra, Coimbra, Portugal
  3. Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal
  4. Hospital and University Center of Coimbra, Coimbra, Portugal
  5. Faculty of Medicine, University of Lisbon, Lisbon, Portugal
  6. Hospital de Santa Maria, Lisbon, Portugal
  7. Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), Coimbra, Portugal

Background: Blood biomarker discovery has been dominated by targeted analysis of disease-associated proteins or conventional untargeted proteomics strategies. However, these attempts have failed to identify high confidence biomarkers of Neurodegenerative Diseases (NDs), which we believe is in part due to: i) the use of conventional proteomics analyses in a very challenging sample, such as blood, and ii) the difficulties in classifying the patients' groups.

Moreover, most of these studies are focused on a single fraction of the blood, such as plasma or serum, which only reveals an incomplete set of circulating proteins. Thus, the present work aimed at obtaining a comprehensive characterization of the circulatory proteins by combining different proteomics analyses of blood samples from the same individuals, including: i) undepleted plasma; ii) peripheral blood mononuclear cells (PBMCs);and iii) high and low molecular weight fractions of the plasma/serum, usually misrepresented in a conventional analysis.

Methodologies: To achieve this goal, state-of-the-art quantitative proteomics, SWATH-MS, was used in the three analyses referred above. These analyses were performed for a representative group of the two most common NDs and a control group. The diagnostic model achieved was further tested in some potential cases of Alzheimer’s and Parkinson’s disease.

Findings: From this combinatory study it was possible to quantify thousands of proteins, with some of these being capable of distinguishing the NDs from the control samples, and AD from PD patients.

Conclusions: The results achieved in this preliminary study strengthened the importance of combining alternative proteomics strategies to obtain a deeper characterization of patient’s samples, creating a “blood signature” of each sample, which has a higher potential as a source of biomarkers. Future work will comprise the introduction of more disease groups (samples are already being collected), and the addition of other analysis such as PTMs-focused and metabolomics analysis of these samples.