Dissecting Brain Pollutant Exposure and its Contribution to Neurodegeneration and Alzheimer’s disease: From Signatures to Prevention Strategies to Protect and Maintain a Healthy Brain

ongoing

Human populations are impregnated by various types of chemical pollutants reported as “hazardous waste” present in the environment. Certain pollutants have adverse effects on brain, but the underlying mechanisms and time-window exposures are still unknown, as well as their contribution on dementia, the 7th leading cause of death. EXPOSIGNALZ project aims to delineate the impact of a selection of environmental pollutants on brain health throughout life and their role in dementia especially Alzheimer’s disease (AD) representing about 70% of dementia cases. Through interdisciplinary approaches, integrating experimental and epidemiological studies, our objectives are to: 1) Identify environmental pollutants likely to have neurotoxic effects and pro-amyloidogenic properties predictive of a neurodegenerative trajectory related to AD using in vitro screening models; 2) Characterize pollutant signatures associated with brain aging and AD in biological matrices of 4 European population-based cohorts of various age groups; 3) Understand the mechanisms of action of pollutants identified in the in vitro screenings and those found in biological signatures, using AD-iPSC and AD preclinical models; 4) Explore the impact of pollutants on early neurodevelopment as a factor of susceptibility for later neurodegenerative diseases using brain organoids and gestational contamination models and 5) Disseminate knowledge to policy makers, to the relevant stakeholders and general public in order to define guidelines for disease prevention and take actions for population’s health. The project, which aims to identify chemical pollutants as new risk factors for dementia as well as new pollutant-associated biomarkers, could contribute to: (i) reduce or delay the incidence of AD, and thus reduce the economic and social burden; and (ii) allow an earlier diagnosis of AD combined with new disease modifying treatments to delay the entrance of patients in the more severe stages of the pathology.