Leader: Licia Iacoviello (NEUROMED); Other collaborator(s): Maria Benedetta Donati (NEUROMED), Elisa Gremese (UNICATT);
Climate change and pollutants exposure may lead to negative health outcomes, and increased mortality. This phenomenon disproportionately affects older people. Task 6.3 will explore the association between climate change parameters (e.g. temperature change) and pollutants exposure (e.g. air and noise pollutants) with functional and clinical parameters in older adults. Meteorological and environmental monitoring data will be analyzed and associated with functional and clinical data from databases identified and implemented in task 1.1 and 1.3
Brief description of the activities and of the intermediate results: Neuromed partner carried out association analyses between the level of several air pollutants measured by ARPA Molise – defined as explained in previous reports – and the incident risk of Parkinson’s disease (PD, defined as above), in the Moli-sani cohort. This revealed a significant association of air pollution PC1 with PD risk, driven by PM10 levels. Moreover, we carried out mediation analyses of several circulating markers, which revealed a prominent role of plateletcrit in the association between PM10 and PD. We reported these findings in the manuscript entitled “Prominent role of PM10 and plateletcrit in the link between air pollution and incident Parkinson’s Disease: findings from a longitudinal Italian population cohort” (currently under review). We are planning the analysis of the influence of chronic exposure to climate change and air pollution on the risk of age-related chronic conditions, prominently neurodegenerative disorders like Parkinson’s disease (defined as above), in collaboration with a team of internationally acknowledged experts in the field – through several meetings and contacts.
The first call for application has been published in April 2024. The deadline to receive the applications is May 3rd 2024. The amount assigned to this topic is € 300.000,00
Main policy, industrial and scientific implications: This activity will lead to a better definition of the association between air pollutant and Parkinson disease in the older population.
A request of new satellite data on four pollutants namely NO2, O3, PM2.5, PM10 with a temporal resolution of 1 year and a spatial resolution of 25x25 m for the time period 2005-2020 has been forwarded to the international EU EXPANSE consortium. The Moli-sani database has been cross-linked with the satellite data available from the EXPANSE consortium - based on a geographically weighted regression (GWR) models interpolating land and satellite data (Shen et al., 2022; doi: 10.1016/j.envint.2022.107485) - and the transfer of the resulting database was made. A preliminary database exploration and quality control of data of the EXPANSE exposures was made, cross-comparing the levels of four different pollutants available - namely NO2, PM10, O3 and PM2.5 The manuscript entitled “Prominent role of PM10 and plateletcrit in the link between air pollution and incident Parkinson’s Disease: findings from a longitudinal Italian population cohort” has been resubmitted to Annals of Neurology.
We have identified the case-cohort subpopulation nested in the Moli-sani study to test the impact and mediation of biochemical and molecular markers on the association between air-pollution and/or climate change and neurodegenerative disease. Serum samples have been retrieved from the Moli-sani biobank and the analysis of biomarkers of neuroinflammation by using the ELLA multiassay system. Buffy coats samples of the Case-cohort sub-sample have been retrieved from the Moli-sani biobank and DNA extraction from buffy coats has been completed and bisulfitation of the DNA is in progress.
To analyse the influence of gene-by-environment interactions on incident neurogenerative (Parkinson’s Disease) risk, we trained a polygenic risk score for PD (PD-PRS) using the SBayesRC method proposed by Zheng et al. (2024; doi: 10.1038/s41588-024-01704-y). The PRS was trained on one of the largest GWAS studies previously published on PD, including 37,688 cases, 18,618 UK Biobank proxy-cases, and 1.4 million controls (Nalls et al. 2019; doi: 10.1016/S1474-4422(19)30320-5). This resulted in a PRS based on 6,749,645 SNPs, available for 23,374 participants with genome-wide array data available after QC and imputation. This score will be tested jointly with air pollutants levels to predict incident PD risk in the Moli-sani cohort.