Environmental micro and nanoparticles in brain affected by FrontoTemporal Dementia: an exposure-driven pathogenesis.

Frontotemporal Dementia (FTD) is characterized by progressive neuronal loss predominantly in the frontal and temporal lobes. Despite decades of research, the initial triggers of neurodegeneration in FTD remain unknown, although abnormal protein aggregates are consistently observed within affected neurons. Autopsy samples from FTD patients were analyzed using Field Emission Gun Environmental Scanning Electron Microscopy (FEG-ESEM) coupled with Energy Dispersive Spectroscopy (EDS), to identify exogenous foreign bodies and characterize their physicochemical nature, proposing an exposome-driven pathogenic model. These techniques enabled higher-resolution imaging and ele-mental analysis than conventional histopathology. The results indicate the systematic presence of exogenous micro- and nanoparticles (NPs) within brain tissue. Their size and composition suggest they can cross the blood-brain barrier. Notably, we observed organic-inorganic aggregates formed by nano-biointeractions between particulate matter and endog-enous proteins. Based on elemental composition, particles were classified as ceramic and metallic debris. The lifelong cumulative exposome - comprising inhaled, ingested, or absorbed environmental particles - may serve as the primary trigger for FTD pathogenesis. We discuss potential mechanisms including nanoparticle interference with neuronal electrical fields, cellular toxicity, and the correlation between particle deposition patterns and clinical symptoms expressed by FTD patients.