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Exposure to air pollutants is known to be an important risk factor in reducing semen quality in men across the world. Poor semen quality results in decline in the global fertility rate and significant personal stress, dysfunctional sexual relationships, and psychosocial problems. Continuous monitoring and effective efforts to reduce air pollution in industries and the environment and making positive changes in daily lifestyle can prevent adverse effects on semen quality and reduce the high prevalence of men infertility. This review aims to summarize studies associating pollutant concentrations of polycyclic aromatic hydrocarbons (PAHs), formaldehyde (FA), and BTEX (benzene, toluene, ethyl-benzene, and xylene) on semen quality. In this systematic review, Scopus, PubMed and Web of Science databases were searched until November 13, 2022. The PECO statement was formulated to clarify the research question, and articles that did not satisfy the criteria outlined in this statement were excluded. Generally, 497 articles were obtained through searching databases, and after the investigations, 26 articles that met the entry criteria were extracted and finally considered in the systematic review. The results showed that occupational and environmental exposures to PAHs, formaldehyde, and BTEX were associated with increased metabolite concentration of toxic pollutants in body fluids. These toxin-associated pollutants directly or indirectly cause detrimental effects on sperm motility, vitality, DNA fragmentation, and morphology. There is evidence on the impact of PAHs, formaldehyde, and BTEX pollutants on the reduction of semen quality. Therefore, proving the relationship between air pollutants and testicular function in semen quality can play an effective role in macro policies and adopting stricter laws to reduce the emission of air pollutants and promote a healthy lifestyle to improve reproductive health in young men.

OBJECTIVE: To investigate the association between family history (FH) of neoplasia, gyneco-obstetric factors and breast cancer (BC) in a case--control study. In cases, to analyze those variables in relation with early onset of BC, the manner of detection (self-examination, prompted by pain, or casual), the size of tumor, and the elapsed time to seek medical attention. MATERIAL AND METHODS: Data from 151 prevalent BC cases and 235 age-matched controls were analyzed by multiple logistic regression, to assess the influence of BC risk factors. RESULTS: Ten per cent of patients and 1% of controls had first-degree relatives (FDR) with BC. Family history of FDR with BC (OR, 11.2; 95% CI 2.42-51.92) or with gastric or pancreatic cancer (OR, 17.7; 95% CI 2.2-142.6) was associated with BC risk. Breastfeeding at or under 25 years of age was protective against BC (OR, 0.40; 95% CI 0.24-0.66). The manner of tumor detection did not influence its size at the time of diagnosis. CONCLUSIONS: Our study confirms that FH of BC and/or of gastric or pancreatic carcinoma are risk factors for BC, while lactation at 25 years of age or earlier is protective.

Metropolitan Mexico City (MMC) children and young adults exhibit overlapping Alzheimer and Parkinsons’ diseases (AD, PD) and TAR DNA-binding protein 43 pathology with magnetic ultrafine particulate matter (UFPM) and industrial nanoparticles (NPs). We studied magnetophoresis, electron microscopy and energy-dispersive X-ray spectrometry in 203 brain samples from 14 children, 27 adults, and 27 ALS cases/controls. Saturation isothermal remanent magnetization (SIRM), capturing magnetically unstable FeNPs ̴ 20nm, was higher in caudate, thalamus, hippocampus, putamen, and motor regions with subcortical vs. cortical higher SIRM in MMC ≤ 40y. Motion behavior was associated with magnetic exposures 25–100 mT and children exhibited IRM saturated curves at 50–300 mT associated to change in NPs position and/or orientation in situ. Targeted magnetic profiles moving under AC/AD magnetic fields could distinguish ALS vs. controls. Motor neuron magnetic NPs accumulation potentially interferes with action potentials, ion channels, nuclear pores and enhances the membrane insertion process when coated with lipopolysaccharides. TEM and EDX showed 7–20 nm NP Fe, Ti, Co, Ni, V, Hg, W, Al, Zn, Ag, Si, S, Br, Ce, La, and Pr in abnormal neural and vascular organelles. Brain accumulation of magnetic unstable particles start in childhood and cytotoxic, hyperthermia, free radical formation, and NPs motion associated to 30–50 μT (DC magnetic fields) are critical given ubiquitous electric and magnetic fields exposures could induce motion behavior and neural damage. Magnetic UFPM/NPs are a fatal brain cargo in children’s brains, and a preventable AD, PD, FTLD, ALS environmental threat. Billions of people are at risk. We are clearly poisoning ourselves.

Background: Hypertrophic pachymeningitis (HP) is a disease with diverse aetiologies, including the autoimmune one, either associated with antineutrophil cytoplasmic antibodies or immunoglobulin G4. Case description: A 65-year-old woman with a history of systemic arterial hypertension, presented with intense progressive headaches. HP and hemispheric vasogenic oedema were observed by nuclear magnetic resonance (NMR) study. During the six months before the headache, she had developed progressive hearing loss which she attributed to age. A biopsy of dura mater showed necrotising vasculitis with peripheral inflammatory infiltrate, made up of accumulations of epithelioid cells and multinucleated giant cells, and abundant eosinophils. A final diagnosis of HP with eosinophilic granulomatosis with polyangiitis (EGPA) was made. Discussion: The patient had eosinophilic granulomatosis with polyangiitis (EGPA) histology, ANCA-negative serology and HP. This case is important because it shows that EGPA seems to have a spectrum of clinical diseases, including HP with negative serology, and bilateral sensorineural hearing loss. Conclusion: We are facing a wide spectrum of EGPA, breaking the paradigm of only systemic involvement.

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 (PM2.5), 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 amyloid1-42, 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?

This Review emphasizes the impact of APOE4—the most significant genetic risk factor for Alzheimer’s disease (AD)—on peripheral and neural effects starting in childhood. We discuss major mechanistic players associated with the APOE alleles’ effects in humans to understand their impact from conception through all life stages and the importance of detrimental, synergistic environmental exposures. APOE4 influences AD pathogenesis, and exposure to fine particulate matter (PM2.5), manufactured nanoparticles (NPs), and ultrafine particles (UFPs) associated with combustion and friction processes appear to be major contributors to cerebrovascular dysfunction, neuroinflammation, and oxidative stress. In the context of outdoor and indoor PM pollution burden—as well as Fe, Ti, and Al alloys; Hg, Cu, Ca, Sn, and Si UFPs/NPs—in placenta and fetal brain tissues, urban APOE3 and APOE4 carriers are developing AD biological disease hallmarks (hyperphosphorylated-tau (P-tau) and amyloid beta 42 plaques (Aβ42)). Strikingly, for Metropolitan Mexico City (MMC) young residents ≤ 40 y, APOE4 carriers have 4.92 times higher suicide odds and 23.6 times higher odds of reaching Braak NFT V stage versus APOE4 non-carriers. The National Institute on Aging and Alzheimer’s Association (NIA-AA) framework could serve to test the hypothesis that UFPs and NPs are key players for oxidative stress, neuroinflammation, protein aggregation and misfolding, faulty complex protein quality control, and early damage to cell membranes and organelles of neural and vascular cells. Noninvasive biomarkers indicative of the P-tau and Aβ42 abnormal protein deposits are needed across the disease continuum starting in childhood. Among the 21.8 million MMC residents, we have potentially 4 million APOE4 carriers at accelerated AD progression. These APOE4 individuals are prime candidates for early neuroprotective interventional trials. APOE4 is key in the development of AD evolving from childhood in highly polluted urban centers dominated by anthropogenic and industrial sources of pollution. APOE4 subjects are at higher early risk of AD development, and neuroprotection ought to be implemented. Effective reductions of PM2.5, UFP, and NP emissions from all sources are urgently needed. Alzheimer’s Disease prevention ought to be at the core of the public health response and physicians-scientist minority research be supported.

Metropolitan Mexico City (MMC) children and young adults exhibit overlapping Alzheimer and Parkinsons' diseases (AD, PD) and TAR DNA-binding protein 43 pathology with magnetic ultrafine particulate matter (UFPM) and industrial nanoparticles (NPs). We studied magnetophoresis, electron microscopy and energy-dispersive X-ray spectrometry in 203 brain samples from 14 children, 27 adults, and 27 ALS cases/controls. Saturation isothermal remanent magnetization (SIRM), capturing magnetically unstable FeNPs ~ 20nm, was higher in caudate, thalamus, hippocampus, putamen, and motor regions with subcortical vs. cortical higher SIRM in MMC = 40y. Motion behavior was associated with magnetic exposures 25-100 mT and children exhibited IRM saturated curves at 50-300 mT associated to change in NPs position and/or orientation in situ. Targeted magnetic profiles moving under AC/AD magnetic fields could distinguish ALS vs. controls. Motor neuron magnetic NPs accumulation potentially interferes with action potentials, ion channels, nuclear pores and enhances the membrane insertion process when coated with lipopolysaccharides. TEM and EDX showed 7-20 nm NP Fe, Ti, Co, Ni, V, Hg, W, Al, Zn, Ag, Si, S, Br, Ce, La, and Pr in abnormal neural and vascular organelles. Brain accumulation of magnetic unstable particles start in childhood and cytotoxic, hyperthermia, free radical formation, and NPs motion associated to 30-50 μT (DC magnetic fields) are critical given ubiquitous electric and magnetic fields exposures could induce motion behavior and neural damage. Magnetic UFPM/NPs are a fatal brain cargo in children's brains, and a preventable AD, PD, FTLD, ALS environmental threat. Billions of people are at risk. We are clearly poisoning ourselves. [ABSTRACT FROM AUTHOR]

Introduction: The annual incidence of brain abscesses is 1-2% in developed countries and up to 8% in developing countries. Our aim was to describe the profile and etiological agents of patients with surgical brain infections according to their nosological diagnosis on admission, and to analyze whether the initial diagnosis influenced the neurological deficit at discharge. Methodology: This was an observational study with convenience sampling. All surgical cases operated between January 2017 and February 2022 with a final diagnosis of an infectious process were included. Three groups were analyzed according to admission diagnosis: a) infection, b) neoplasia, and c) miscellaneous. The time before admission, final histological diagnosis, etiological agent, length of hospital stay, and secondary neurological deficits were investigated. Descriptive and comparative statistics were used. Results: 24 cases, including 18 (75%) men and 6 (25%) women, of ages 19 to 61 years (average 43.7 years) were studied. Nosological diagnoses on admission were infection in 9 (37.5%) patients, cerebral neoplasia in 9 (37.5%) patients, and miscellaneous diagnoses in 6 (25%) patients. Among the miscellaneous, neoplastic, and infectious groups, 33.3%, 33.3%, and 22.2% of patients were discharged with some neurological deficits with overall neurological morbidity and mortality of 29.6% and 8%, respectively. The etiological agents were Mycobacterium tuberculosis (16.6%), Streptococcus sp. (13%), Morganella morganii (8.7%), Nocardia sp. (4.3%), Cryptococcus sp. (4.3%), and Klebsiella sp. (4.3%). Conclusions: Nosological diagnosis on admission did not influence the percentage of patients with neurological deficits in our study. Mycobacterium was the most frequent etiological agent. [ABSTRACT FROM AUTHOR]

Exposure to metals is ubiquitous and emission sources include gasoline, diesel, smoke from wildfires, contaminated soil, water and food, medical implants, waste recycling facilities, subway exposures, and occupational environments. PM2.5 exposure is associated with impaired cognitive performance, neurobehavioral alterations, incidence of dementia, and Alzheimer's disease (AD) risk. Heavy-duty diesel vehicles are major emitters of metal-rich PM2.5 and nanoparticles in Metropolitan Mexico City (MMC). Cognitive impairment was investigated in 336 clinically healthy, middle-class, Mexican volunteers, age 29.2 ± 13.3 years with 13.7 ± 2.4 years of education using the Montreal Cognitive Assessment (MoCA). MoCA scores varied with age and residency in three Mexican cities with cognition deficits impacting ~74% of the young middle-class population (MoCA ≤ 25). MMC residents ≥31 years (x¯46.2 ± 11.8 y) had MoCA x¯20.4 ± 3.4 vs. low pollution controls 25.2 ± 2.4 (p < 0.0001). Formal education years positively impacted MoCA total scores across all participants (p < 0.0001). Residency in PM2.5 polluted cities impacts multi-domain cognitive performance. Identifying and making every effort to lower key pollutants impacting neural risk trajectories and monitoring cognitive longitudinal performance are urgent. PM2.5 emission control should be prioritized, metal emissions targeted, and neuroprevention interventions implemented early.

Subependymal giant cell astrocytoma (SEGA), a circumscribed grade I glioma, is typically associated with tuberous sclerosis complex (TSC). However, "solitary SEGA" has been described. We performed a systematic review of available case reports and case series of solitary SEGA. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was used with the following MeSH terms: "Subependymal giant cell astrocytoma," "Sporadic," "Absence," "Non-associated," "Solitary," and "Tuberous Sclerosis." Data sources included PubMed, Google Scholar, Web of Science, and Cochrane from 1979 to June 29, 2023. Of the 546 studies, 20 met the inclusion criteria. Fifty-nine cases were analyzed. The mean age was 19 years (range 4–75), with 29 women (49.1%). Tumor ranged in size from 0.8 to 5.8 cm. Headache was the most frequent initial symptom (75.6%). The lateral ventricles near the foramen of Monro were the most common location (66.10%). Tumors expressed neuroglial (n = 19) or only glial (n = 20) markers. In nine of 59 cases, genetic studies ruled out germinal TSC1/2 mutations; in 13 cases (22.03%), somatic mutations in those genes were identified. "Solitary SEGAs" included tumors with neuroglial profile and classic morphological pattern, and tumors with only glial markers. It is necessary to confirm in SEGA-like tumors, the dual nature with at least glial fibrillary acidic protein (GFAP), neurofilaments, and synaptophysin antibodies. Screening for TSC1/2 mutations, and probably of the NF type 1 gene, is recommended for both germline and somatic mutations. Long-term clinical follow-up is necessary to analyze biological behavior and compare it with genetic and molecular profiles. [ABSTRACT FROM AUTHOR]

Objective: To compare clinicopathological characteristics of patients with solitary subependymal giant cell astrocytoma (SEGA) at our institution, with those associated to tuberous sclerosis complex (TSC). Methods: It was a descriptive-retrospective study of surgically treated SEGA patients (2013-2022). Demographic and clinical data were obtained. An immunohistochemistry (IHC) panel was applied: GFAP, neurofilaments, hamartin, tuberin, Ki67, nestin, OCT-4, INI-1, STAT-6, CK-AE1/ AE3, TTF1, and YAP-1. Descriptive statistical was used. Results: 4 patients were studied: Two women, 23 and 25 years old, diagnosed as TSC patients at 10 and 12 years of age, and two men with solitary SEGA (18 and 46 years old). Tumors were positive to GFAP, NF, nestin, and TTF1. Cytoplasmic STAT6 and CK stains was observed in all patients. 2/4 cases showed YAP-1 nuclear expression. TSC patients retained INI-1 nuclear expression, while solitary SEGAs lost it. Conclusions: SEGA is a glioneuronal tumor that expresses markers of neuroepithelial stem cells and cytokeratins. Its diagnosis must be supported with a minimal IHC panel: GFAP, neurofilaments, synaptophysin, nestin and TTF1. Morphological differences were observed between the TSC related and solitary SEGAs and in INI1 expression. Nuclear expression of YAP-1 in 2/4 tumors, opens the possibility of research for combined use of YAP and mTOR regulators in the management of SEGA. [ABSTRACT FROM AUTHOR]

Environmental exposures to fine particulate matter (PM2.5) and ultrafine particle matter (UFPM) are associated with overlapping Alzheimer’s, Parkinson’s and TAR DNA-binding protein 43 (TDP-43) hallmark protein pathologies in young Metropolitan Mexico City (MMC) urbanites. We measured CSF concentrations of TDP-43 in 194 urban residents, including 92 MMC children aged 10.2 ± 4.7 y exposed to PM2.5 levels above the USEPA annual standard and to high UFPM and 26 low pollution controls (11.5 ± 4.4 y); 43 MMC adults (42.3 ± 15.9 y) and 14 low pollution adult controls (33.1 ± 12.0 y); and 19 amyotrophic lateral sclerosis (ALS) patients (52.4 ± 14.1 y). TDP-43 neuropathology and cisternal CSF data from 20 subjects—15 MMC (41.1 ± 18.9 y) and 5 low pollution controls (46 ± 16.01 y)—were included. CSF TDP-43 exponentially increased with age (p < 0.0001) and it was higher for MMC residents. TDP-43 cisternal CSF levels of 572 ± 208 pg/mL in 6/15 MMC autopsy cases forecasted TDP-43 in the olfactory bulb, medulla and pons, reticular formation and motor nuclei neurons. A 16 y old with TDP-43 cisternal levels of 1030 pg/mL exhibited TDP-43 pathology and all 15 MMC autopsy cases exhibited AD and PD hallmarks. Overlapping TDP-43, AD and PD pathologies start in childhood in urbanites with high exposures to PM2.5 and UFPM. Early, sustained exposures to PM air pollution represent a high risk for developing brains and MMC UFPM emissions sources ought to be clearly identified, regulated, monitored and controlled. Prevention of deadly neurologic diseases associated with air pollution ought to be a public health priority and preventive medicine is key.

Abstract Background Germline mutations in E‐cadherin (CDH1) gene are associated with autosomal‐dominantly inherited cancer syndrome characterized by diffuse gastric cancer, lobular breast cancer, and in some families, cleft lip/palate. However, there may be generations in which these neoplasms do not occur at all in a family and later on, one or another carcinoma arises, which makes it difficult for physicians to think about hereditary origin. Methods We report the first Mexican family with CDH1 mutation (variant c.377del). Results An asymptomatic young woman underwent a search for mutations in susceptibility genes for breast cancer due to the history of this neoplasm in her mother and maternal aunt. A CDH1 mutation was detected. After an endoscopy, a diffuse gastric carcinoma was found. Later on, three generations of this family were studied. The findings are presented. Conclusion Medical communities should be aware of the contribution of this gene in the development of hereditary diffuse gastric carcinoma (HDGC) and breast cancer.

Exposures to fine particulate matter PM2.5 are associated with Alzheimer’s, Parkinson’s (AD, PD) and TDP-43 pathology in young Metropolitan Mexico City (MMC) residents. High-resolution structural T1-weighted brain MRI and/or Montreal Cognitive Assessment (MoCA) data were examined in 302 volunteers age 32.7 ± 6.0 years old. We used multivariate linear regressions to examine cortical surface area and thickness, subcortical and cerebellar volumes and MoCA in ≤30 vs. ≥31 years old. MMC residents were exposed to PM2.5 ~ 30.9 µg/m3. Robust hemispheric differences in frontal and temporal lobes, caudate and cerebellar gray and white matter and strong associations between MoCA total and index scores and caudate bilateral volumes, frontotemporal and cerebellar volumetric changes were documented. MoCA LIS scores are affected early and low pollution controls ≥ 31 years old have higher MoCA vs. MMC counterparts (p ≤ 0.0001). Residency in MMC is associated with cognitive impairment and overlapping targeted patterns of brain atrophy described for AD, PD and Fronto-Temporal Dementia (FTD). MMC children and young adult longitudinal studies are urgently needed to define brain development impact, cognitive impairment and brain atrophy related to air pollution. Identification of early AD, PD and FTD biomarkers and reductions on PM2.5 emissions, including poorly regulated heavy-duty diesel vehicles, should be prioritized to protect 21.8 million highly exposed MMC urbanites.

Quadruple aberrant hyperphosphorylated tau, beta-amyloid, α-synuclein and TDP-43 neuropathology and metal solid nanoparticles (NPs) are documented in the brains of children and young adults exposed to Metropolitan Mexico City (MMC) pollution. We investigated environmental NPs reaching noradrenergic and dopaminergic nuclei and the cerebellum and their associated ultrastructural alterations. Here, we identify NPs in the locus coeruleus (LC), substantia nigrae (SN) and cerebellum by transmission electron microscopy (TEM) and energy-dispersive X-ray spectrometry (EDX) in 197 samples from 179 MMC residents, aged 25.9 ± 9.2 years and seven older adults aged 63 ± 14.5 years. Fe, Ti, Hg, W, Al and Zn spherical and acicular NPs were identified in the SN, LC and cerebellar neural and vascular mitochondria, endoplasmic reticulum, Golgi, neuromelanin, heterochromatin and nuclear pore complexes (NPCs) along with early and progressive neurovascular damage and cerebellar endothelial erythrophagocytosis. Strikingly, FeNPs 4 ± 1 nm and Hg NPs 8 ± 2 nm were seen predominantly in the LC and SN. Nanoparticles could serve as a common denominator for misfolded proteins and could play a role in altering and obstructing NPCs. The NPs/carbon monoxide correlation is potentially useful for evaluating early neurodegeneration risk in urbanites. Early life NP exposures pose high risk to brains for development of lethal neurologic outcomes. NP emissions sources ought to be clearly recognized, regulated, and monitored; future generations are at stake.

Anthropogenic ultrafine particulate matter (UFPM) and industrial and natural nanoparticles (NPs) are ubiquitous. Normal term, preeclamptic, and postconceptional weeks(PCW) 8–15 human placentas and brains from polluted Mexican cities were analyzed by TEM and energy-dispersive X-ray spectroscopy. We documented NPs in maternal erythrocytes, early syncytiotrophoblast, Hofbauer cells, and fetal endothelium (ECs). Fetal ECs exhibited caveolar NP activity and widespread erythroblast contact. Brain ECs displayed micropodial extensions reaching luminal NP-loaded erythroblasts. Neurons and primitive glia displayed nuclear, organelle, and cytoplasmic NPs in both singles and conglomerates. Nanoscale Fe, Ti, and Al alloys, Hg, Cu, Ca, Sn, and Si were detected in placentas and fetal brains. Preeclamptic fetal blood NP vesicles are prospective neonate UFPM exposure biomarkers. NPs are reaching brain tissues at the early developmental PCW 8–15 stage, and NPs in maternal and fetal placental tissue compartments strongly suggests the placental barrier is not limiting the access of environmental NPs. Erythroblasts are the main early NP carriers to fetal tissues. The passage of UFPM/NPs from mothers to fetuses is documented and fingerprinting placental single particle composition could be useful for postnatal risk assessments. Fetal brain combustion and industrial NPs raise medical concerns about prenatal and postnatal health, including neurological and neurodegenerative lifelong consequences.

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 (PM2.5), 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 amyloid1-42, 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 weaiting for? [ABSTRACT FROM AUTHOR]