The activity of PROPAG-AGEING partners has been focused on:
1. The achievement of the ethical approvals both for the discovery and the validation phase. Each partner has submitted a formal request to the competent Ethical Commission to ask for the permission of share and analyse PROPAG-AGEING samples. In addition, the four centers that will recruit the siblings of PD patients (AUSL-ISNB, UMG-GOE, SAS and UCL) have asked for the relative permission. Recruitment will be performed according to a protocol opportunely standardised between the 4 recruiting centers. Finally, both the discovery and validation studies have been deposited in the the German Clinical Trials Register (DRKS) and are publicly available at the following links: https://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00009427 ;
https://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00011260(se abrirá en una nueva ventana) 2. The set-up of the PROPAG-AGEING database. To allow a comprehensive analysis of the clinical and demographical data of the samples, the partners have agreed to upload the data in common database. The database is password-protected and the information are completely anonymized, in order to accomplish with the current privacy standards.
3. The harmonization of the existing cohorts and selection of the samples to be analysed in the discovery phase. The data deriving from the different cohorts have been harmonized in order to make comparable the measurements deriving from different recruitments and collections. In addition, imaging data from PD patients produced in different centers have been compared and normalized in order to perform statistical analyses. Finally, the partners have chosen the subjects with the most informative phenotypes within each cohort.
4. Meta-analysis on demographic and clinical characteristics of PROPAG-AGEING samples
5. The set-up of the experimental approaches for the analysis of the samples.
6. The genomic, epigenomic, metabolomic, proteomic, transcriptomic, miRNomic characterization of the selected samples and their validation in additional samples/by different approaches
7. The blood analaysis of target biomarkers in selected samples
8. The reprogramming of dermal fibroblasts from centenarians and PD patients to iPSCs cells and their differentiation to dopaminergic neurons
9. The analysis of neuroimaging data from PD patients
10. The development of analytical tools for the comprehensive analysis of clinical and experimental data
11. The recruitment of 340 siblings of PD patients.
12. The gut microbioata analysis of the siblings of PD patients.
Collectively, our results suggest that while peripheral (blood and serum) biomarkers of age do not detect age-acceleration effects in de novo PD patients, biomarkers specific for the CNS identify deviations compared to the aging trajectories. Furthermore, an alteration of inflammatory pathways is found at the peripheral level. Finally, PROPAG-AGEING had the merit to recruit a large, multi-center cohort of sibslings of PD patients, a cohort of extremely high value for the early diagnosis and progression of the disease. These results have been disseminated mainly to colleagues within the scientific community, in the framework of several worldwide meetings and in several scientific publications.
