title: Early Alzheimer's and Parkinson's disease pathology in urban children: Friend versus Foe responses--it is time to face the evidence.
abstract: Chronic exposure to particulate matter air pollution is known to cause inflammation leading to respiratory- and cardiovascular-related sickness and death. Mexico City Metropolitan Area children exhibit an early brain imbalance in genes involved in oxidative stress, inflammation, and innate and adaptive immune responses. Early dysregulated neuroinflammation, brain microvascular damage, production of potent vasoconstrictors, and perturbations in the integrity of the neurovascular unit likely contribute to progressive neurodegenerative processes. The accumulation of misfolded proteins coincides with the anatomical distribution observed in the early stages of both Alzheimer's and Parkinson's diseases. We contend misfolding of hyperphosphorylated tau (HPπ), alpha-synuclein, and beta-amyloid could represent a compensatory early protective response to the sustained systemic and brain inflammation. However, we favor the view that the chronic systemic and brain dysregulated inflammation and the diffuse vascular damage contribute to the establishment of neurodegenerative processes with childhood clinical manifestations. Friend turns Foe early; therefore, implementation of neuroprotective measures to ameliorate or stop the inflammatory and neurodegenerative processes is warranted in exposed children. Epidemiological, cognitive, structural, and functional neuroimaging and mechanistic studies into the association between air pollution exposures and the development of neuroinflammation and neurodegeneration in children are of pressing importance for public health.
authors.affiliation: Center for Structural and Functional Neurosciences, The University of Montana, 32 Campus Drive, Skaggs Building 287, Missoula, MT 59812, USA. lilian.calderon-garciduenas@umontana.edu
authors.forename: Lilian
authors.initials: L
authors.lastname: Calderón-Garcidueñas
authors.forename: Maricela
authors.initials: M
authors.lastname: Franco-Lira
authors.forename: Antonieta
authors.initials: A
authors.lastname: Mora-Tiscareño
authors.forename: Humberto
authors.initials: H
authors.lastname: Medina-Cortina
authors.forename: Ricardo
authors.initials: R
authors.lastname: Torres-Jardón
authors.forename: Michael
authors.initials: M
authors.lastname: Kavanaugh
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000397:Air Pollution / Q000009:adverse effects*; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000209:etiology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002648:Child; D002947:Cities; D005260:Female; D006801:Humans; D008297:Male; D008800:Mexico; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000175:diagnosis* / Q000209:etiology; D052638:Particulate Matter; D017510:Protein Folding; D014505:Urban Population; D055815:Young Adult; D051844:alpha-Synuclein / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D052638:Particulate Matter; D051844:alpha-Synuclein; D016875:tau Proteins