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Exposures to fine particulate matter PM2.5 and ozone O3 are associated with Alzheimer's disease (AD) risk. Mexico City residents have lifetime exposures to PM2.5 and O3 above annual USEPA standards and their brains contain high redox, combustion, and friction-derived magnetite nanoparticles. AD pathological changes with subcortical pre-tangle stages in infancy and cortical tau pre-tangles, NFT Stages I-II, and amyloid phases 1-2 are identified by the 2nd decade. Given their AD continuum, a reliable identification of cognitive impairment is of utmost importance. The Montreal Cognitive Assessment (MoCA) was administered to 517 urbanites, age 21.60±5.88 years, with 13.69±1.28 formal education years, in Mexican PM2.5 polluted cities. MoCA score was 23.92±2.82, and 24.7% and 30.3% scored ≤24 and ≤22, respectively (MCI≤24, AD≤22). Cognitive deficits progressively targeted Visuospatial, Executive, Language, and Memory domains, body mass index (BMI) impacting total scores negatively (p = 0.0008), aging driving down Executive, Visuospatial, and Language index scores (p < 0.0001, 0.0037, and 0.0045), and males performing better in Executive tasks. Average age for AD MoCA scores was 22.38±7.7 years. Residency in polluted cities is associated with progression of multi-domain cognitive impairment affecting 55% of Mexican seemingly healthy youth. Normal BMI ought to be a neuroprotection goal. MoCA provides guidance for further mandatory neuropsychological testing in young populations. Identifying and lowering key neurotoxicants impacting neural risk trajectories in the developing brain and monitoring cognitive performance would greatly facilitate multidisciplinary early diagnosis and prevention of AD in high risk young populations. Cognitive deficits hinder development of those representing the force moving the country in future years. [ABSTRACT FROM AUTHOR]

Exposure to fine particulate matter (PM2.5) and ozone (O3) above US EPA standards is associated with Alzheimer's disease (AD) risk, while Mn toxicity induces parkinsonism. Mexico City Metropolitan Area (MCMA) children have pre- and postnatal sustained and high exposures to PM2.5, O3, polycyclic aromatic hydrocarbons, and metals. Young MCMA residents exhibit frontal tau hyperphosphorylation and amyloid-β (Aβ)1 - 42 diffuse plaques, and aggregated and hyperphosphorylated α-synuclein in olfactory nerves and key brainstem nuclei. We measured total prion protein (TPrP), total tau (T-tau), tau phosphorylated at threonine 181 (P-Tau), Aβ1-42, α-synuclein (t-α-syn and d-α-synuclein), BDNF, insulin, leptin, and/or inflammatory mediators, in 129 normal CSF samples from MCMA and clean air controls. Aβ1-42 and BDNF concentrations were significantly lower in MCMA children versus controls (p = 0.005 and 0.02, respectively). TPrP increased with cumulative PM2.5 up to 5 μg/m3 and then decreased, regardless of cumulative value or age (R2 = 0.56). TPrP strongly correlated with T-Tau and P-Tau, while d-α-synuclein showed a significant correlation with TNFα, IL10, and IL6 in MCMA children. Total synuclein showed an increment in childhood years related to cumulated PM2.5, followed by a decrease after age 12 years (R2 = 0.47), while d-α-synuclein exhibited a tendency to increase with cumulated PM2.5 (R2 = 0.30). CSF Aβ1-42, BDNF, α-synuclein, and TPrP changes are evolving in young MCMA urbanites historically showing underperformance in cognitive processes, odor identification deficits, downregulation of frontal cellular PrP, and neuropathological AD and PD hallmarks. Neuroprotection of young MCMA residents ought to be a public health priority. [ABSTRACT FROM AUTHOR]

Millions of children are exposed to concentrations of air pollutants, including fine particulate matter (PM2.5), above safety standards. In the Mexico City Metropolitan Area (MCMA) megacity, children show an early brain imbalance in oxidative stress, inflammation, innate and adaptive immune response-associated genes, and blood-brain barrier breakdown. We investigated serum and cerebrospinal fluid (CSF) antibodies to neural and tight junction proteins and environmental pollutants in 139 children ages 11.91 ± 4.2 y with high versus low air pollution exposures. We also measured metals in serum and CSF. MCMA children showed significantly higher serum actin IgG, occludin/zonulin 1 IgA, IgG, myelin oligodendrocyte glycoprotein IgG and IgM (p < 0.01), myelin basic protein IgA and IgG, S-100 IgG and IgM, and cerebellar IgG (p < 0.001). Serum IgG antibodies to formaldehyde, benzene, and bisphenol A, and concentrations of Ni and Cd were significantly higher in exposed children (p < 0.001). CSF MBP antibodies and nickel concentrations were higher in MCMA children (p = 0.03). Air pollution exposure damages epithelial and endothelial barriers and is a robust trigger of tight junction and neural antibodies. Cryptic 'self' tight junction antigens can trigger an autoimmune response potentially contributing to the neuroinflammatory and Alzheimer and Parkinson's pathology hallmarks present in megacity children. The major factor determining the impact of neural antibodies is the integrity of the blood-brain barrier. Defining the air pollution linkage of the brain/immune system interactions and damage to physical and immunological barriers with short and long term neural detrimental effects to children's brains ought to be of pressing importance for public health. [ABSTRACT FROM AUTHOR]