Abstract
Fronto Temporal Dementia is characterized by progressive neuronal loss predominantly in the frontal and temporal lobes. Despite decades of research, the initial triggers of neurodegeneration in Frontotemporal Dementia remain unknown, although abnormal protein aggregates are consistently observed within affected neurons. Autopsy samples from Fronto Temporal Dementia patients were analyzed using Field Emission Gun Environmental Scanning Electron Microscopy coupled with Energy Dispersive Spectroscopy, to identify the presence of exogenous foreign bodies and characterize their physicochemical nature, proposing an exposome-driven pathogenic model. These techniques enabled higher-resolution imaging and elemental analysis than conventional histopathology.
The results indicate the systematic presence of exogenous micro- and nanoparticles 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 endogenous proteins. Based on elemental composition, particles were classified as ceramic (Silicates, Titania, Zirconia, etc), metallic debris (stainless-steel, Antimony) and rare earths (Lanthanum, Neodymium, etc). The lifelong cumulative exposome — comprising inhaled, ingested, or absorbed environmental particles — may serve as the primary trigger for Fronto Temporal Dementia 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 Frontotemporal Dementia patients.