Long-term air pollution exposure is associated with neuroinflammation, an altered innate immune response, disruption of the blood-brain barrier, ultrafine particulate deposition, and accumulation of amyloid β-42 and α-synuclein in children and young adults

Lilian Calderón-Garcidueñas, Anna C. Solt, Carlos Henríquez-Roldán, Ricardo Torres-Jardón, Bryan Nuse, Lou Herritt, Rafael Villarreal-Calderón, Norma Osnaya, Ida Stone, Raquel García, Diane M. Brooks, Angelica González-Maciel, Rafael Reynoso-Robles, Ricardo Delgado-Chávez, William Reed

Research output: Contribution to journalArticlepeer-review

773 Scopus citations

Abstract

Air pollution is a serious environmental problem. We investigated whether residency in cities with high air pollution is associated with neuroinflammation/neurodegeneration in healthy children and young adults who died suddenly. We measured mRNA cyclooxygenase-2, interleukin-1β, and CD14 in target brain regions from low (n = 12) or highly exposed residents (n = 35) aged 25.1 ± 1.5 years. Upregulation of cyclooxygenase-2, interleukin-1β, and CD14 in olfactory bulb, frontal cortex, substantia nigrae and vagus nerves; disruption of the blood-brain barrier; endothelial activation, oxidative stress, and inflammatory cell trafficking were seen in highly exposed subjects. Amyloid β42 (Aβ42) immunoreactivity was observed in 58.8% of apolipoprotein E (APOE) 3/3 < 25 y, and 100% of the APOE 4 subjects, whereas α-synuclein was seen in 23.5% of < 25 y subjects. Particulate material (PM) was seen in olfactory bulb neurons, and PM < 100 nm were observed in intraluminal erythrocytes from lung, frontal, and trigeminal ganglia capillaries. Exposure to air pollution causes neuroinflammation, an altered brain innate immune response, and accumulation of Aβ42 and α-synuclein starting in childhood. Exposure to air pollution should be considered a risk factor for Alzheimer's and Parkinson's diseases, and carriers of the APOE 4 allele could have a higher risk of developing Alzheimer's disease if they reside in a polluted environment.

Original languageEnglish
Pages (from-to)289-310
Number of pages22
JournalToxicologic Pathology
Volume36
Issue number2
DOIs
StatePublished - Feb 2008

Keywords

  • Air pollution
  • Alzheimer's disease
  • Amyloid β42
  • Neuroinflammation
  • Parkinson's disease
  • Ultrafine particulate matter
  • α-synuclein

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