BRAIN-CLIMA: Investigating the Combined Impact of Heat and Air Pollution on Blood-Brain Barrier Integrity and Brain Aging in Latin America

BRAIN-CLIMA is a transdisciplinary project investigating how heat stress affects brain health, and whether people in areas of higher air pollution are particularly vulnerable. The project aims to identify biomarkers for and elucidate the mechanistic links between these stressors and brain damage in populations across Latin America. We hypothesize that heat stress exposure disrupts blood-brain barrier (BBB) integrity, an early pathomechanism contributing to brain inflammation, aging, cognitive decline and neurodegeneration, and that this effect is exacerbated by air pollution and interactions with other factors, including socioeconomic status and comorbidities. Leveraging several cohorts in Latin America, which integrates harmonized, multimodal, and georeferenced cohort data from 7 countries (2010-2025), we will analyze environmental, clinical, and biospecimen data to identify early warning signs and point of no return for neurodegeneration. In work stream (WS)-1, we will assess heat-related, PM2.5-modified, blood- and extracellular vesicle-based biomarkers of BBB and brain damage. In WS-2, we will develop computational aging clocks of cognitive function, and brain aging linking exposure to climate-related stressors and socioeconomic disparity to accelerated aging. In WS-3, by integrating mechanistic and epidemiological insights, we will generate evidence to inform climate mitigation policies that protect brain health and identify novel interventions including early warning systems.