Abstract
The neuropathological hallmarks of Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal lobar degeneration (FTLD), and amyotrophic lateral sclerosis (ALS) are present in urban children exposed to fine particulate matter (PM(2.5)), combustion and friction ultrafine PM (UFPM), and industrial nanoparticles (NPs). Metropolitan Mexico City (MMC) forensic autopsies strongly suggest that anthropogenic UFPM and industrial NPs reach the brain through the nasal/olfactory, lung, gastrointestinal tract, skin, and placental barriers. Diesel-heavy unregulated vehicles are a key UFPM source for 21.8 million MMC residents. We found that hyperphosphorylated tau, beta amyloid(1-42), α-synuclein, and TAR DNA-binding protein-43 were associated with NPs in 186 forensic autopsies (mean age 27.45 ± 11.89 years). The neurovascular unit is an early NPs anatomical target, and the first two decades of life are critical: 100% of 57 children aged 14.8 ± 5.2 years had AD pathology; 25 (43.9%) AD+TDP-43; 11 (19.3%) AD + PD + TDP-43; and 2 (3.56%) AD +PD. Fe, Ti, Hg, Ni, Co, Cu, Zn, Cd, Al, Mg, Ag, Ce, La, Pr, W, Ca, Cl, K, Si, S, Na, and C NPs are seen in frontal and temporal lobes, olfactory bulb, caudate, substantia nigra, locus coeruleus, medulla, cerebellum, and/or motor cortical and spinal regions. Endothelial, neuronal, and glial damages are extensive, with NPs in mitochondria, rough endoplasmic reticulum, the Golgi apparatus, and lysosomes. Autophagy, cell and nuclear membrane damage, disruption of nuclear pores and heterochromatin, and cell death are present. Metals associated with abrasion and deterioration of automobile catalysts and electronic waste and rare earth elements, i.e., lanthanum, cerium, and praseodymium, are entering young brains. Exposure to environmental UFPM and industrial NPs in the first two decades of life are prime candidates for initiating the early stages of fatal neurodegenerative diseases. MMC children and young adults-surrogates for children in polluted areas around the world-exhibit early AD, PD, FTLD, and ALS neuropathological hallmarks forecasting serious health, social, economic, academic, and judicial societal detrimental impact. Neurodegeneration prevention should be a public health priority as the problem of human exposure to particle pollution is solvable. We are knowledgeable of the main emission sources and the technological options to control them. What are we waiting for?