Early Alzheimer’s and Parkinson’s Disease Pathology in Urban Children: Friend versus Foe Responses—It Is Time to Face the Evidence

Abstract

Chronic exposure to particulate matter air pollution is known to cause inflammation leading to respiratory- and cardiovascular-related sickness and death. Mexico City Metropolitan Area children exhibit an early brain imbalance in genes involved in oxidative stress, inflammation, and innate and adaptive immune responses. Early dysregulated neuroinflammation, brain microvascular damage, production of potent vasoconstrictors, and perturbations in the integrity of the neurovascular unit likely contribute to progressive neurodegenerative processes. The accumulation of misfolded proteins coincides with the anatomical distribution observed in the early stages of both Alzheimer's and Parkinson's diseases. We contend misfolding of hyperphosphorylated tau (HPπ), alpha-synuclein, and beta-amyloid could represent a compensatory early protective response to the sustained systemic and brain inflammation. However, we favor the view that the chronic systemic and brain dysregulated inflammation and the diffuse vascular damage contribute to the establishment of neurodegenerative processes with childhood clinical manifestations. Friend turns Foe early; therefore, implementation of neuroprotective measures to ameliorate or stop the inflammatory and neurodegenerative processes is warranted in exposed children. Epidemiological, cognitive, structural, and functional neuroimaging and mechanistic studies into the association between air pollution exposures and the development of neuroinflammation and neurodegeneration in children are of pressing importance for public health.

Mexico City normal weight children exposed to high concentrations of ambient PM2.5 show high blood leptin and endothelin-1, vitamin D deficiency, and food reward hormone dysregulation versus low pollution controls. Relevance for obesity and Alzheimer disease

“…In the setting of severe air pollution, a serious concern is vitamin D deficiency in close association with indoor confinement during the day, residency at higher altitudes, darker skin pigmentation and poor nutritional intake (Alvaer et al, 2007;Balasubramanian and Ganesh, 2008;Calderón-Garcidueñas et al, 2013a, 2013bChristakos et al, 2013;Kelishadi et al, 2014;Miñ-ambres et al, 2014). Vitamin D deficiency in Metropolitan Mexico City area (MCMA) children is important because well-known metabolic and dementia links (Annweiler et al, 2013;Anastasiou et al, 2014;Bishnoi et al, 2014;Bartali et al, 2014).…”

“…The APOE ε4 allele is the strongest known genetic risk factor for late and early onset AD (Michaelson, 2014;Huang and Mahley, 2014), and given our previous reports of Mexico City APOE 4 young carriers accelerating their expression of AD neuropathological markers (Calderón-Garcidueñas et al, 2008a, 2008b, 2010, 2012a, 2012b, 2013a, 2013b, APOE genotyping was included in this work. Likewise, high concentrations of endothelin-1 (ET-1), a marker of endothelial dysfunction and exposure to severe air pollution obligated its inclusion (Calderón-Garcidueñas et al, 2007).…”

The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability

“…Finally, the presence of nanoparticulate matter in such environments may also be a source of neuropathology per se whether coated in mycotoxins or not [313,314]. These authors have demonstrated that such nanoparticles passage into the brain via the olfactory epithelium and the olfactory bulb lead to increased production of inducible nitric oxide synthase (iNOS), NF-ΚB, and TNFα and the deposition of beta amyloid plaques highly reminiscent of the pattern seen in Alzheimer's disease [314,315]. These authors also reported the results of a disturbing study examining the effects of the polluted air of Mexico City on the brains of local children.…”

Olfactory transport efficiency of the manganese oxide nanoparticles (II) after their single or multiple intranasal administrations

“…Так, одним из первых симптомов развития ряда деменций (болезнь Паркинсона, болезнь Альцгей-мера и др.) является нарушение восприятия запаховых стимулов, поэтому воздействия факторов среды, в том числе компонентов вдыхаемых аэрозолей, рассматривают в качестве возможных экологических факторов риска для данных заболеваний (CalderónGarcidueñas et al, 2013).…”