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

TLDR

Air pollution is a serious environmental problem. The study examined whether living in highly polluted cities is linked to neuroinflammation or neurodegeneration in healthy children and young adults who died suddenly. Researchers quantified mRNA levels of cyclooxygenase‑2, interleukin‑1β, and CD14 in specific brain regions of low‑ and high‑exposure residents (n = 47, mean age ≈ 25 yr). High‑pollution exposure was associated with increased expression of cyclooxygenase‑2, interleukin‑1β, and CD14 in olfactory bulb, frontal cortex, substantia nigra, and vagus nerve, along with blood‑brain barrier disruption, endothelial activation, oxidative stress, inflammatory cell trafficking, deposition of ultrafine particulate matter, and accumulation of amyloid‑β42 and α‑synuclein, suggesting that air pollution may elevate the risk of Alzheimer’s and Parkinson’s disease, particularly in APOE 4 carriers.

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.