Particulate matter and co-occurring genetic risk induce oxidative stress and cardiac and brain Alzheimer’s pathology

Amyloid-beta (Aβ) aggregates, an Alzheimer’s disease (AD) pathological hallmark, extend beyond the brain to the heart of heart failure (HF) and AD patients. Being diseases of the elderly, increased prevalence is expected as the population ages. However, changes in the incidence and prevalence of dementia over the past decades, and the independent association of exposure to air particulate matter (PM) with poor cognitive function, adverse cardiovascular effects, and oxidative stress hint to the contribution of other factors beyond senescence. Therefore we evaluate whether, and by which mechanism(s), PM exposure affects heart and brain proteinopathy with/without genetic predisposition. AD-prone and control mice are exposed for three months to filtered air (FA) or concentrated ambient PM < 2.5μm in diameter (PM2.5), and evaluated for Aβ pathology, cognitive and cardiac function, and markers of oxidative stress. Aβ pathology become noticeable in AD hearts and worsens with PM2.5 in AD brains. Functionally, PM2.5 lead to anxiety and memory deficits and worsens diastolic function. Redox homeostasis is negatively impacted by genotype and PM2.5. This study identifies environmental pollution as a potential key contributor to early progression of heart and brain proteinopathy, delineating a crucial timepoint for early interventions to limit multiorgan damage in vulnerable patients. (Figure presented.)