Cerebrospinal fluid biomarkers in highly exposed PM2.5 urbanites: The risk of Alzheimer's and parkinson's diseases in Young Mexico City Residents

Lilian Calderón-Garciduẽnas, José Avila-Ramírez, Ana Calderón-Garciduẽnas, Tonatiuh González-Heredia, Hilda Acũna-Ayala, Chih kai Chao, Charles Thompson, Rubén Ruiz-Ramos, Victor Cortés-González, Luz Martínez-Martínez, Mario Alberto García-Pérez, Jacques Reis, Partha S. Mukherjee, Ricardo Torres-Jardón, Ingolf Lachmann

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

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.

Original languageEnglish
Title of host publicationAlzheimer's Disease and Air Pollution
Subtitle of host publicationThe Development and Progression of a Fatal Disease from Childhood and the Opportunities for Early Prevention
PublisherIOS Press
Pages477-493
Number of pages17
ISBN (Electronic)9781643681597
ISBN (Print)9781643681580
DOIs
StatePublished - May 3 2021

Keywords

  • Air pollution
  • Alzheimer's disease
  • Amyloid-ß
  • BDNF
  • Cerebrospinal fluid
  • Children
  • Insulin
  • Leptin
  • Mexico city
  • Parkinson
  • PM
  • Prion cellular protein
  • α-synuclein

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