Workplan

The general aim of PROPAG-AGEING is to identify the combination of specific cellular and molecular alterations and pathways capable of shifting the phenotype of elderly subjects from a physiological decline to clinically overt PD to eventually identify markers of early PD diagnosis (before motor symptoms occur) using blood and other body fluids.

To attain this ambitious objective, PROPAG-AGEING work plan includes:

  1. Harmonization of data from existing cohorts of PD patients and healthy subjects. We will put together biological samples and data from about 700 de novo PD patients, 860 healthy controls and 1000 long-living subjects, previously collected by PROPAG-AGEING partners.
  2. Discovery phase. We will perform a comprehensive characterization of a representative number of de novo PD patients by a panel of -omic technologies. These data will be compared with the reference cohort of centenarians and centenarian offspring, that has been thoroughly characterized with the same omics and that will be used as multi-dimensional gold standard of healthy ageing.
  3. Validation phase. The candidate molecular signatures resulting from the discovery phase will be validated in a larger number of PD patients and long-living subjects and in a newly recruited cohort of subjects who are siblings of PD patients but who are not affected by this disease. This approach will allow us to verify the specificity and the predictive power of the putative markers, as well as their capability to be associated with healthy ageing (protective markers).
  4. Comprehensive analysis and data integration. We will use a systems biology approach to identify the combination of specific cellular and molecular pathways that deviate from the trajectory of healthy ageing towards the development of PD, possibly useful for PD diagnosis.
  5. Functional validation. We will perform in vitro studies on dopaminergic neurons obtained by re-programming induced-Pluripotent Stem Cells (iPSC) derived from skin fibroblasts of de novo PD patients, in comparison with those obtained from centenarians. This model will allow us to study, in controlled conditions, the role of the identified biomarkers in PD.

Workplan