RECALL will determine how emerging chemical exposures—particularly pesticides and PFAS—shape brain health and brain ageing across the life course, with a particular focus on women’s vulnerability and resilience during the menopausal transition. The project targets overlooked windows of susceptibility, including pregnancy, the menopausal transition, and midlife, as well as at-risk groups such as individuals with preclinical Alzheimer’s disease (AD). By reprocessing over 20,000 untargeted high-resolution mass spectrometry (HRMS) datasets and linking them with existing biospecimens and outcomes measured over up to 25 years of follow-up, RECALL will identify previously unrecognised neurotoxicants while delivering targeted analyses of priority chemicals in novel matrices such as hair, indicative of cumulative exposures. New follow-ups in women and a deeply phenotyped AD clinical panel will strengthen coverage of vulnerable life stages and BBB-related neurovascular vulnerability. Integrated with harmonised cognitive assessments, neuroimaging, and the largest blood-based CNS biomarker resource to date (≈7,000 individuals), this unique resource will enable life-course analyses of brain ageing trajectories. Mechanistic studies, including matched postmortem brain and CSF analyses, a validated blood–brain barrier-on-chip model, and microbiome–metabolomics approaches, will clarify pathways of toxicity and identify modifiable protective factors, including microbial, hormonal, metabolic, and social resilience pathways. By leveraging already collected cohort data, RECALL ensures a cost-efficient, time-effective design with exceptional longitudinal depth. The project will deliver robust epidemiological and mechanistic evidence, FAIR datasets, validated workflows, and policy-ready guidance to reduce the brain health impacts of pollution for public authorities, clinicians, and citizens.
This project has received funding from the European Union’s Horizon Europe research and innovation programme.
