Prolonged exposure to air pollution leads to genetic changes in rat brains, study finds: Insight into potential health effects of dirty air in the Los Angeles basin -- ScienceDaily

Prolonged exposure to particulate matter in
air pollution in the Los Angeles Basin triggered inflammation and the
appearance of cancer-related genes in the brains of rats, a Cedars-Sinai
study has found.

While previous research has documented the association between air
pollution and a variety of diseases, including cancer, the study found
markers indicating certain materials in coarse air pollution -- nickel,
in particular -- may play a role in genetic changes related to disease
development, said Julia Ljubimova, MD, PhD.

Hallmarks of Alzheimer disease are evolving relentlessly in Metropolitan Mexico City infants, children and young adults. APOE4 carriers have higher suicide risk and higher odds of reaching NFT stage V at ≤ 40 years of age - ScienceDirect

Exposures to fine particulate matter (PM_2.5) and ozone (O₃)
above USEPA standards are associated with Alzheimer's disease (AD)
risk. Metropolitan Mexico City (MMC) residents have life time exposures
to PM_2.5 and O₃ above USEPA standards. We
investigated AD intra and extracellular protein aggregates and
ultrastructural neurovascular pathology in 203 MMC residents age
25.36 ± 9.23 y. Immunohistochemical methods were used to identify AT8
hyperphosphorilated tau (Htau) and 4G8 (amyloid β 17-24). Primary
outcomes: staging of Htau and amyloid, per decade and cumulative PM_2.5 (CPM_2.5) above standard. Apolipoprotein E allele 4 (APOE4), age and cause of death were secondary outcomes.

Subcortical
pretangle stage b was identified in an 11month old baby. Cortical tau
pre-tangles, neurofibrillary tangles (NFT) Stages I-II, amyloid phases
1–2, Htau in substantia nigrae, auditory, oculomotor, trigeminal and
autonomic systems were identified by the 2nd decade. Progression to NFT
stages III-V was present in 24.8% of 30–40 y old subjects. APOE4
carriers have 4.92 times higher suicide odds (p = 0.0006), and 23.6
times higher odds of NFT V (p < 0.0001) v APOE4 non-carriers having
similar CPM_2.5 exposure and age. Age (p = 0.0062) and CPM_2.5 (p = 0.0178) were significant for developing NFT V. Combustion-derived nanoparticles
were associated with early and progressive damage to the neurovascular
unit. Alzheimer's disease starting in the brainstem of young children
and affecting 99.5% of young urbanites is a serious health crisis. Air pollution control
should be prioritised. Childhood relentless Htau makes a fundamental
target for neuroprotective interventions and the first two decades are
critical. We recommend the concept of preclinical AD be revised and
emphasize the need to define paediatric environmental, nutritional,
metabolic and genetic risk factor interactions of paramount importance
to prevent AD. AD evolving from childhood is threating the wellbeing of
our children and future generations.

Translational Psychiatry - Particulate air pollutants, APOE alleles and their contributions to cognitive impairment in older women and to amyloidogenesis in experimental models

 Exposure to particulate matter (PM) in the ambient air and its interactions with APOE alleles may contribute to the acceleration of brain aging and the pathogenesis of Alzheimer’s disease (AD). Neurodegenerative effects of particulate air pollutants were examined in a US-wide cohort of older women from the Women’s Health Initiative Memory Study (WHIMS) and in experimental mouse models. Residing in places with fine PM exceeding EPA standards increased the risks for global cognitive decline and all-cause dementia respectively by 81 and 92%, with stronger adverse effects in APOE ε4/4 carriers. Female EFAD transgenic mice (5xFAD+/−/human APOE ε3 or ε4+/+) with 225 h exposure to urban nanosized PM (nPM) over 15 weeks showed increased cerebral β-amyloid by thioflavin S for fibrillary amyloid and by immunocytochemistry for Aβ deposits, both exacerbated by APOE ε4. Moreover, nPM exposure increased Aβ oligomers, caused selective atrophy of hippocampal CA1 neurites, and decreased the glutamate GluR1 subunit. Wildtype C57BL/6 female mice also showed nPM-induced CA1 atrophy and GluR1 decrease. In vitro nPM exposure of neuroblastoma cells (N2a-APP/swe) increased the pro-amyloidogenic processing of the amyloid precursor protein (APP). We suggest that airborne PM exposure promotes pathological brain aging in older women, with potentially a greater impact in ε4 carriers. The underlying mechanisms may involve increased cerebral Aβ production and selective changes in hippocampal CA1 neurons and glutamate receptor subunits.

Autism genes are selectively targeted by environmental pollutants including pesticides, heavy metals, bisphenol A, phthalates and many others in food, cosmetics or household products

The increasing incidence of autism suggests a major environmental influence. Epidemiology has implicated many candidates and genetics many susceptibility genes. Gene/environment interactions in autism were analysed using 206 autism susceptibility genes (ASG's) from the Autworks database to interrogate ∼1 million chemical/gene interactions in the comparative toxicogenomics database. Any bias towards ASG's was statistically determined for each chemical. Many suspect compounds identified in epidemiology, including tetrachlorodibenzodioxin, pesticides, particulate matter, benzo(a)pyrene, heavy metals, valproate, acetaminophen, SSRI's, cocaine, bisphenol A, phthalates, polyhalogenated biphenyls, flame retardants, diesel constituents, terbutaline and oxytocin, inter alia showed a significant degree of bias towards ASG's, as did relevant endogenous agents (retinoids, sex steroids, thyroxine, melatonin, folate, dopamine, serotonin). Numerous other suspected endocrine disruptors (over 100) selectively targeted ASG's including paraquat, atrazine and other pesticides not yet studied in autism and many compounds used in food, cosmetics or household products, including tretinoin, soy phytoestrogens, aspartame, titanium dioxide and sodium fluoride. Autism polymorphisms influence the sensitivity to some of these chemicals and these same genes play an important role in barrier function and control of respiratory cilia sweeping particulate matter from the airways. Pesticides, heavy metals and pollutants also disrupt barrier and/or ciliary function, which is regulated by sex steroids and by bitter/sweet taste receptors. Further epidemiological studies and neurodevelopmental and behavioural research is warranted to determine the relevance of a large number of suspect candidates whose addition to the environment, household, food and cosmetics might be fuelling the autism epidemic in a gene-dependent manner.

Cerebrospinal Fluid Biomarkers in Highly Exposed PM2.5 Urbanites: The Risk of Alzheimer’s and Parkinson’s Diseases in Young Mexico City Residents - IOS Press

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."