title: Cerebrospinal Fluid Biomarkers in Highly Exposed PM2.5 Urbanites: The Risk of Alzheimer's and Parkinson's Diseases in Young Mexico City Residents.
abstract: 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.
authors: The University of Montana, Missoula, MT, USA.|Universidad del Valle de México, México.
authors: Lilian
authors: L
authors: Calderón-Garcidueñas
authors: Médica Sur, Mexico City, México.
authors: José
authors: J
authors: Avila-Ramírez
authors: Instituto de Medicina Forense, Universidad Veracruzana, Boca del Río, México.
authors: Ana
authors: A
authors: Calderón-Garcidueñas
authors: Universidad del Valle de México, México.
authors: Tonatiuh
authors: T
authors: González-Heredia
authors: Universidad del Valle de México, México.
authors: Hilda
authors: H
authors: Acuña-Ayala
authors: The University of Montana, Missoula, MT, USA.
authors: Chih-Kai
authors: CK
authors: Chao
authors: The University of Montana, Missoula, MT, USA.
authors: Charles
authors: C
authors: Thompson
authors: Instituto de Medicina Forense, Universidad Veracruzana, Boca del Río, México.
authors: Rubén
authors: R
authors: Ruiz-Ramos
authors: Hospital de Especialidades No. 14, I.M.S.S, Boca del Río, México.
authors: Victor
authors: V
authors: Cortés-González
authors: Hospital de Especialidades No. 14, I.M.S.S, Boca del Río, México.
authors: Luz
authors: L
authors: Martínez-Martínez
authors: Hospital Regional de Alta Especialidad, Ciudad Victoria, Tamaulipas, México.
authors: Mario Alberto
authors: MA
authors: García-Pérez
authors: Service de Neurologie, Centre Hospitalier Universitaire, Hôpital de Hautepierre, Strasbourg, France.
authors: Jacques
authors: J
authors: Reis
authors: Mathematics Department, Boise State University, Boise, ID, USA.
authors: Partha S
authors: PS
authors: Mukherjee
authors: Universidad Nacional Autónoma de México, Mexico City, México.
authors: Ricardo
authors: R
authors: Torres-Jardón
authors: AJ Roboscreen GmbH, Leipzig, Germany.
authors: Ingolf
authors: I
authors: Lachmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000397:Air Pollution / Q000009:adverse effects; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000453:epidemiology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D019208:Brain-Derived Neurotrophic Factor / Q000134:cerebrospinal fluid; D002648:Child; D002947:Cities / Q000453:epidemiology; D006801:Humans; D008800:Mexico / Q000453:epidemiology; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000453:epidemiology*; D052638:Particulate Matter / Q000009:adverse effects*; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D010865:Pilot Projects; D011446:Prospective Studies; D014505:Urban Population; D055815:Young Adult; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D052638:Particulate Matter; D010446:Peptide Fragments; D051844:alpha-Synuclein; C075222:amyloid beta-protein (1-42); C579455:BDNF protein, human
keywords: Air pollution; Alzheimer’s disease; BDNF; Mexico City; PM2.5; Parkinson; amyloid-β1–42; cerebrospinal fluid; children; insulin; leptin; prion cellular protein; α-synuclein