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 beta-42 and alpha-synuclein in children and young adults.
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-1beta, 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-1beta, 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 beta42 (Abeta42) immunoreactivity was observed in 58.8% of apolipoprotein E (APOE) 3/3 < 25 y, and 100% of the APOE 4 subjects, whereas alpha-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 Abeta42 and alpha-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.
Calderón-Garcidueñas
Lilian
L
Instituto Nacional de Pediatría, Mexico City, Mexico. lilian.calderon-garciduenas@umontana.edu
Solt
Anna C
AC
Henríquez-Roldán
Carlos
C
Torres-Jardón
Ricardo
R
Nuse
Bryan
B
Herritt
Lou
L
Villarreal-Calderón
Rafael
R
Osnaya
Norma
N
Stone
Ida
I
García
Raquel
R
Brooks
Diane M
DM
González-Maciel
Angelica
A
Reynoso-Robles
Rafael
R
Delgado-Chávez
Ricardo
R
Reed
William
W
D000293:Adolescent; D000328:Adult; D000393:Air Pollutants / Q000009:adverse effects*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004660:Encephalitis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009830:Olfactory Bulb / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D052638:Particulate Matter / Q000009:adverse effects; D010446:Peptide Fragments / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D014504:Urban Health; D014630:Vagus Nerve / Q000187:drug effects / Q000473:pathology; D051844:alpha-Synuclein / Q000378:metabolism*
D000393:Air Pollutants; D016229:Amyloid beta-Peptides; C508585:IL1B protein, human; D053583:Interleukin-1beta; D018950:Lipopolysaccharide Receptors; D052638:Particulate Matter; D010446:Peptide Fragments; D012333:RNA, Messenger; D051844:alpha-Synuclein; C075222:amyloid beta-protein (1-42); D051546:Cyclooxygenase 2