Combustion-Derived Nanoparticles in Key Brain Target Cells and Organelles in Young Urbanites: Culprit Hidden in Plain Sight in Alzheimer’s Disease Development

González-Maciel, Angélica; Reynoso-Robles, Rafael; Torres‐Jardón, Ricardo; Mukherjee, Partha S.; Calderón‐Garcidueñas, Lilian

doi:10.3233/jad-170012

Cited by 99 publications

(55 citation statements)

References 123 publications

(232 reference statements)

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“…Of all air pollutants, particles are thought to be the most important inhaled toxicants in urban air, 11 particularly in relation to brain damage. 12 Among the various particle types, we found airborne copper to be associated with tissue modifications and functional connectivity in the caudate nucleus in children. 13 Other metals, such as iron, have been linked to structural changes in mice brain, 14 and environmental Fe nanoparticles were found in brain tissue.…”

Section: Pollution?mentioning

confidence: 81%

Pre‐natal brain development as a target for urban air pollution

Sunyer

Dadvand

2019

Basic Clin Pharma Tox

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Air pollution is the main urban‐related environmental hazard and one of the major contributors to the global burden of disease based on its cardiovascular‐respiratory impacts. In children, exposure to urban air pollution is associated, among others, with decelerated neurodevelopment early in life and increased risk of neurodevelopmental problems such as attention‐deficit hyperactivity disorder, autism spectrum disorders, academic failure and the start of Alzheimer's pathogenesis. However, the evidence of the effects of air pollution on brain development is still inadequate, mainly due to the limitations in (a) characterizing brain development (most studies were based on subjective tools such as questionnaires or neuropsychological tests) and (b) air pollution exposure (most studies only used residential levels based on geographical modelling and also overlooking the variation in the mixture of air pollutants as well as the composition and hence toxicity of particulate pollutants in different settings), (c) the lack of studies during the most vulnerable stages of brain development (foetal and early life (first two years post‐natally)) and (d) the lack of structural and functional imaging data underlying these effects. In mice, in utero exposure to fine particles was linked to structural brain changes and there is a need to establish the generalizability of these findings in human beings. Though scarce, current evidence in children supports the importance of the pre‐natal period as a susceptible window of exposure. Two studies in schoolchildren found that pre‐natal air pollution exposure might damage brain structure while exposure during childhood was not linked to any structural alteration. Another study showed that children with higher traffic‐related air pollution at school had lower functional integration in key brain networks, but no changes in brain structure, possibly partly because of the time window of air pollution exposure (in utero versus childhood exposure). A key development is to discover the windows of greatest sensitivity of structural brain changes to air pollution exposure by incorporating the recent advances in non‐invasive imaging to characterize natal and post‐natal brain development and exploring whether and to what extend placental dysfunction could mediate such an association. Studying pre‐natal life is important because effects at this time are of a potentially irreversible nature and because the largest preventive opportunities occur during these periods.

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Section: Pollution?mentioning

confidence: 81%

Pre‐natal brain development as a target for urban air pollution

Sunyer

Dadvand

2019

Basic Clin Pharma Tox

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“…degenerating cortical neurons, apoptotic white matter glial cells, NFT, and BBB impairment) in the brains of demented dogs living in a highly air polluted urban region of Mexico City (Calderon-Garciduenas et al, 2002). Subsequent studies by the same group have documented numerous early pathological indicators of neurodegenerative diseases, including accumulation of Aβ42, oxidative stress, neuroinflammation, and neurovascular damage in the brains of children and young people in Mexico City experiencing chronic exposure to high levels of air pollution and PM2.5 (Calderon-Garciduenas et al, 2004, 2008, 2012Gonzalez-Maciel et al, 2017). Consistently, epidemiological studies support significant association of chronic exposure to PM2.5 or traffic-related air pollution with increased risk to dementia and AD (Kioumourtzoglou et al, 2016;Chen et al, 2017;Fu et al, 2019) and age-related cerebral atrophy (Wilker et al, 2015).…”

Section: Pm25 Exposure Induces Predisposition To Dementia Ad and Amentioning

confidence: 99%

Predisposition to Alzheimer’s and Age-Related Brain Pathologies by PM2.5 Exposure: Perspective on the Roles of Oxidative Stress and TRPM2 Channel

et al. 2020

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Accumulating epidemiological evidence supports that chronic exposure to ambient fine particular matters of <2.5 µm (PM2.5) predisposes both children and adults to Alzheimer's disease (AD) and age-related brain damage leading to dementia. There is also experimental evidence to show that PM2.5 exposure results in early onset of AD-related pathologies in transgenic AD mice and development of AD-related and age-related brain pathologies in healthy rodents. Studies have also documented that PM2.5 exposure causes AD-linked molecular and cellular alterations, such as mitochondrial dysfunction, synaptic deficits, impaired neurite growth, neuronal cell death, glial cell activation, neuroinflammation, and neurovascular dysfunction, in addition to elevated levels of amyloid β (Aβ) and tau phosphorylation. Oxidative stress and the oxidative stress-sensitive TRPM2 channel play important roles in mediating multiple molecular and cellular alterations that underpin AD-related cognitive dysfunction. Documented evidence suggests critical engagement of oxidative stress and TRPM2 channel activation in various PM2.5-induced cellular effects. Here we discuss recent studies that favor causative relationships of PM2.5 exposure to increased AD prevalence and AD-and age-related pathologies, and raise the perspective on the roles of oxidative stress and the TRPM2 channel in mediating PM2.5-induced predisposition to AD and age-related brain damage.

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“…Olfactory mucosa—containing axons directly exposed to the external environment—provides a direct route from the olfactory system to the CNS. Agents, such as bacteria, viruses, prions, nanoparticles, and heavy metals, can damage the olfactory endothelium, thereby entering the brain via the olfactory mucosa . Air pollution may promote microbial infiltration of the brain either indirectly by residential nasal microbes that take advantage of inorganic‐pollution‐associated damage to nasal epithelia, or directly by airborne microbes that cross from nasal cavity to CNS with microbial barrier breach not relying on barrier damage by inorganic compounds.…”

Section: Nasal Cavity and Respiratory Tractmentioning

confidence: 99%

Alzheimer's disease and symbiotic microbiota: an evolutionary medicine perspective

Fox

Knorr

Haptonstall

2019

Annals of the New York Academy of Sciences

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Microorganisms resident in our bodies participate in a variety of regulatory and pathogenic processes. Here, we describe how etiological pathways implicated in Alzheimer's disease (AD) may be regulated or disturbed by symbiotic microbial activity. Furthermore, the composition of symbiotic microbes has changed dramatically across human history alongside the rise of agriculturalism, industrialization, and globalization. We postulate that each of these lifestyle transitions engendered progressive depletion of microbial diversity and enhancement of virulence, thereby enhancing AD risk pathways. It is likely that the human life span extended into the eighth decade tens of thousands of years ago, yet little is known about premodern geriatric epidemiology. We propose that microbiota of the gut, oral cavity, nasal cavity, and brain may modulate AD pathogenesis, and that changes in the microbial composition of these body regions across history suggest escalation of AD risk. Dysbiosis may promote immunoregulatory dysfunction due to inadequate education of the immune system, chronic inflammation, and epithelial barrier permeability. Subsequently, proinflammatory agents—and occasionally microbes—may infiltrate the brain and promote AD pathogenic processes. APOE genotypes appear to moderate the effect of dysbiosis on AD risk. Elucidating the effect of symbiotic microbiota on AD pathogenesis could contribute to basic and translational research.

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Combustion-Derived Nanoparticles in Key Brain Target Cells and Organelles in Young Urbanites: Culprit Hidden in Plain Sight in Alzheimer’s Disease Development

Cited by 99 publications

References 123 publications

Pre‐natal brain development as a target for urban air pollution

Pre‐natal brain development as a target for urban air pollution

Predisposition to Alzheimer’s and Age-Related Brain Pathologies by PM2.5 Exposure: Perspective on the Roles of Oxidative Stress and TRPM2 Channel

Alzheimer's disease and symbiotic microbiota: an evolutionary medicine perspective

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