Air Pollution, Combustion and Friction Derived Nanoparticles, and Alzheimer’s Disease in Urban Children and Young Adults

2021 ◽  
Author(s):  
Lilian Calderón-Garcidueñas ◽  
Angélica González-Maciel ◽  
Randy J. Kulesza ◽  
Luis Oscar González-González ◽  
Rafael Reynoso-Robles ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Air Pollution ◽  
Young Adults ◽  
Particulate Matter ◽  
Mexico City ◽  
Neurofibrillary Tangle ◽  
Rapid Progression ◽  
Us Epa ◽  
Children And Young Adults

Exposures to fine particulate matter (PM2.5) and ozone (O3)≥US EPA standards are associated with Alzheimer’s disease (AD) risk. The projection of 13.8 million AD cases in the US by the year 2050 obligate us to explore early environmental exposures as contributors to AD risk and pathogenesis. Metropolitan Mexico City children and young adults have lifetime exposures to PM2.5 and O3, and AD starting in the brainstem and olfactory bulb is relentlessly progressing in the first two decades of life. Magnetite combustion and friction-derived nanoparticles reach the brain and are associated with early and progressive damage to the neurovascular unit and to brain cells. In this review: 1) we highlight the interplay environment/genetics in the AD development in young populations; 2) comment upon ApoE ε4 and the rapid progression of neurofibrillary tangle stages and higher suicide risk in youth; and 3) discuss the role of combustion-derived nanoparticles and brain damage. A key aspect of this review is to show the reader that air pollution is complex and that profiles change from city to city with common denominators across countries. We explore and compare particulate matter profiles in Mexico City, Paris, and Santiago in Chile and make the point of why we should invest in decreasing PM2.5 to at least our current US EPA standard. Multidisciplinary intervention strategies are critical for prevention or amelioration of cognitive deficits and AD progression and risk of suicide in young individuals. AD pathology evolving from childhood is threating the wellbeing of future generations.

Air Pollution, Combustion and Friction Derived Nanoparticles, and Alzheimer’s Disease in Urban Children and Young Adults

2019 ◽  
Vol 70 (2) ◽  
pp. 343-360 ◽  
Author(s):  
Lilian Calderón-Garcidueñas ◽  
Angélica González-Maciel ◽  
Randy J. Kulesza ◽  
Luis Oscar González-González ◽  
Rafael Reynoso-Robles ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Air Pollution ◽  
Young Adults ◽  
Urban Children ◽  
Children And Young Adults

Apolipoprotein E4, Gender, Body Mass Index, Inflammation, Insulin Resistance, and Air Pollution Interactions: Recipe for Alzheimer’s Disease Development in Mexico City Young Females

2021 ◽  
Author(s):  
Lilian Calderón-Garcidueñas ◽  
Suzanne M. de la Monte
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Air Pollution ◽  
High Risk ◽  
Mexico City ◽  
Cognitive Deficits ◽  
Central Nervous System Involvement ◽  
High Risk Group ◽  
Polycyclic Aromatic

Given the epidemiological trends of increasing Alzheimer’s disease (AD) and growing evidence that exposure and lifestyle factors contribute to AD risk and pathogenesis, attention should be paid to variables such as air pollution, in order to reduce rates of cognitive decline and dementia. Exposure to fine particulate matter (PM2.5) and ozone (O3) above the US EPA standards is associated with AD risk. Mexico City children experienced pre- and postnatal high exposures to PM2.5, O3, combustion-derived iron-rich nanoparticles, metals, polycyclic aromatic hydrocarbons, and endotoxins. Exposures are associated with early brain gene imbalance in oxidative stress, inflammation, innate and adaptive immune responses, along with epigenetic changes, accumulation of misfolded proteins, cognitive deficits, and brain structural and metabolic changes. The Apolipoprotein E (APOE) 4 allele, the most prevalent genetic risk for AD, plays a key role in the response to air pollution in young girls. APOE 4 heterozygous females with >75% to <94% BMI percentiles are at the highest risk of severe cognitive deficits (1.5–2 SD from average IQ). This review focused on the relationships between gender, BMI, systemic and neural inflammation, insulin resistance, hyperleptinemia, dyslipidemia, vascular risk factors, and central nervous system involvement in APOE4 urbanites exposed to PM2.5 and magnetite combustion-derived iron-rich nanoparticles that can reach the brain. APOE4 young female heterozygous carriers constitute a high-risk group for a fatal disease: AD. Multidisciplinary intervention strategies could be critical for prevention or amelioration of cognitive deficits and long-term AD progression in young individuals at high risk.

A Critical Proton MR Spectroscopy Marker of Alzheimer’s Disease Early Neurodegenerative Change: Low Hippocampal NAA/Cr Ratio Impacts APOE ε4 Mexico City Children and Their Parents

2021 ◽  
Author(s):  
Lilian Calderón-Garcidueñas ◽  
Antonieta Mora-Tiscareño ◽  
Gastón Melo-Sánchez ◽  
Joel Rodríguez-Díaz ◽  
Ricardo Torres-Jardón ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Air Pollution ◽  
Mexico City ◽  
Density Functional ◽  
Fine Particulate Matter ◽  
Healthy Children ◽  
1H Mrs ◽  
Apoe Ε4 ◽  
The Right

Severe air pollution exposures produce systemic, respiratory, myocardial, and brain inflammation and Alzheimer’s disease (AD) hallmarks in clinically healthy children. We tested whether hippocampal metabolite ratios are associated with contrasting levels of air pollution, APOE, and body mass index (BMI) in paired healthy children and one parent sharing the same APOE alleles. We used 1H-MRS to interrogate bilateral hippocampal single-voxel in 57 children (12.45 ± 3.4 years) and their 48 parents (37.5 ± 6.78 years) from a low pollution city versus Mexico City (MC). NAA/Cr, Cho/Cr, and mI/Cr metabolite ratios were analyzed. The right hippocampus NAA/Cr ratio was significantly different between cohorts (p = 0.007). The NAA/Cr ratio in right hippocampus in controls versus APOE ε4 MC children and in left hippocampus in MC APOE ε4 parents versus their children was significantly different after adjusting for age, gender, and BMI (p = 0.027 and 0.01, respectively). The NAA/Cr ratio is considered reflective of neuronal density/functional integrity/loss of synapses/higher pTau burden, thus a significant decrease in hippocampal NAA/Cr ratios may constitute a spectral marker of early neurodegeneration in young urbanites. Decreases in NAA/Cr correlate well with cognitive function, behavioral symptoms, and dementia severity; thus, since the progression of AD starts decades before clinical diagnosis, our findings support the hypothesis that under chronic exposures to fine particulate matter and ozone above the standards, neurodegenerative processes start in childhood and APOE ε4 carriers are at higher risk. Gene and environmental factors are critical in the development of AD and the identification and neuroprotection of young urbanites at high risk must become a public health priority.

Ozone, Particulate Matter, and Newly Diagnosed Alzheimer’s Disease: A Population-Based Cohort Study in Taiwan

2021 ◽  
Author(s):  
Chau-Ren Jung ◽  
Yu-Ting Lin ◽  
Bing-Fang Hwang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Air Pollution ◽  
Cohort Study ◽  
Particulate Matter ◽  
Proportional Hazards ◽  
Newly Diagnosed ◽  
Hazards Model

Several studies with animal research associate air pollution in Alzheimer’s disease (AD) neuropathology, but the actual impact of air pollution on the risk of AD is unknown. Here, this study investigates the association between long-term exposure to ozone (O3) and particulate matter (PM) with an aerodynamic diameter equal to or less than 2.5 μm (PM2.5), and newly diagnosed AD in Taiwan. We conducted a cohort study of 95,690 individuals’ age ≥ 65 during 2001–2010. We obtained PM10 and O3 data from Taiwan Environmental Protection Agency during 2000–2010. Since PM2.5 data is only accessible entirely after 2006, we used the mean ratio between PM2.5 and PM10 during 2006–2010 (0.57) to estimate the PM2.5 concentrations from 2000 to 2005. A Cox proportional hazards model was used to evaluate the associations between O3 and PM2.5 at baseline and changes of O3 and PM2.5 during the follow-up period and AD. The adjusted HR for AD was weakly associated with a raised concentration in O3 at baseline per increase of 9.63 ppb (adjusted HR 1.06, 95% confidence interval (CI) 1.00–1.12). Further, we estimated a 211% risk of increase of AD per increase of 10.91 ppb in O3 over the follow-up period (95% CI 2.92–3.33). We found a 138% risk of increase of AD per increase of 4.34 μg/m3 in PM2.5 over the follow-up period (95% CI 2.21–2.56). These findings suggest long-term exposure to O3 and PM2.5 above the current US EPA standards are associated with increased the risk of AD.

Prefrontal white matter pathology in air pollution exposed Mexico City young urbanites and their potential impact on neurovascular unit dysfunction and the development of Alzheimer's disease

2016 ◽  
Vol 146 ◽  
pp. 404-417 ◽  
Author(s):  
Lilian Calderón-Garcidueñas ◽  
Rafael Reynoso-Robles ◽  
Javier Vargas- Martínez ◽  
Aline Gómez-Maqueo-Chew ◽  
Beatriz Pérez-Guillé ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Air Pollution ◽  
White Matter ◽  
Mexico City ◽  
Neurovascular Unit ◽  
Potential Impact ◽  
White Matter Pathology

scholarly journals Growing evidence links air pollution exposure to risk of Alzheimer’s disease and related dementia

Brain ◽  
2019 ◽  
Vol 143 (1) ◽  
pp. 8-10
Author(s):  
Melinda C Power
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Air Pollution ◽  
Particulate Matter ◽  
Episodic Memory ◽  
Memory Decline ◽  
Air Pollution Exposure ◽  
Pollution Exposure

This scientific commentary refers to ‘Particulate matter and episodic memory decline mediated by early neuroanatomic biomarkers of Alzheimer’s disease’, by Younan et al. (doi: 10.1093/brain/awz348).

The Use of Standardized Diesel Exhaust Particles in Alzheimer’s Disease Research

2021 ◽  
pp. 1-2
Author(s):  
Michelle L. Block ◽  
Urmila P. Kodavanti
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Air Pollution ◽  
Particulate Matter ◽  
Diesel Exhaust ◽  
Disease Risk ◽  
Urban Air Pollution ◽  
Diesel Exhaust Particles ◽  
Urban Air ◽  
Exhaust Particles

The mechanisms underlying how urban air pollution exposure conveys Alzheimer’s disease risk and affects plaque pathology is largely unknown. Because particulate matter, the particle component of urban air pollution, varies across location, pollution source, and time, a single model representative of all ambient particulate matter is unfeasible for research investigating the role of ar pollution in central nervous system diseases. More specifically, the investigation of several models of particulate matter with enrichment of source-specific components are essential to employ, in order to more fully understand what characteristics of particulate matter affects Alzheimer’s disease, including standardized diesel exhaust particles.

Increased Gain in the Auditory Pathway, Alzheimer’s Disease Continuum, and Air Pollution: Peripheral and Central Auditory System Dysfunction Evolves Across Pediatric and Adult Urbanites

2021 ◽  
Author(s):  
Lilian Calderón-Garcidueñas ◽  
Randy J. Kulesza ◽  
Yusra Mansour ◽  
Mario Aiello-Mora ◽  
Partha S. Mukherjee ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Air Pollution ◽  
Young Adults ◽  
Evoked Potentials ◽  
Auditory Evoked Potentials ◽  
Auditory Pathway ◽  
Conduction Time ◽  
Brainstem Auditory Evoked Potentials ◽  
Noninvasive Biomarkers

A major impediment in early diagnosis of Alzheimer’s disease (AD) is the lack of robust non-invasive biomarkers of early brain dysfunction. Metropolitan Mexico City (MMC) children and young adults show hyperphosphorylated tau, amyloid-β, and α-synuclein within auditory and vestibular nuclei and marked dysmorphology in the ventral cochlear nucleus and superior olivary complex. Based on early involvement of auditory brainstem centers, we believe brainstem auditory evoked potentials can provide early AD biomarkers in MMC young residents. We measured brainstem auditory evoked potentials in MMC clinically healthy children (8.52 ± 3.3 years) and adults (21.08 ± 3.0 years, 42.48 ± 8.5 years, and 71.2 ± 6.4 years) compared to clean air controls (6.5 ± 0.7 years) and used multivariate analysis adjusting for age, gender, and residency. MMC children had decreased latency to wave I, delays in waves III and V, and longer latencies for interwave intervals, consistent with delayed central conduction time of brainstem neural transmission. In sharp contrast, young adults have significantly shortened interwave intervals I–III and I–V. By the 5th decade, wave V and interval I–V were significantly shorter, while the elderly cohort had significant delay in mean latencies and interwave intervals. Compensatory plasticity, increased auditory gain, cochlear synaptopathy, neuroinflammation, and AD continuum likely play a role in the evolving distinct auditory pathology in megacity urbanites. Understanding auditory central and peripheral dysfunction in the AD continuum evolving and progressing in pediatric and young adult populations may shed light on the complex mechanisms of AD development and help identify strong noninvasive biomarkers. AD evolving from childhood in air pollution environments ought to be preventable.

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

2021 ◽  
Author(s):  
Angélica González-Maciel ◽  
Rafael Reynoso-Robles ◽  
Ricardo Torres-Jardón ◽  
Partha S. Mukherjee ◽  
Lilian Calderón-Garcidueñas
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Young Adults ◽  
Choroid Plexus ◽  
Short Term Memory ◽  
Close Contact ◽  
Fine Particulate Matter ◽  
Brain Inflammation ◽  
Children And Young Adults ◽  
Brain Target

Millions of children and young adults are exposed to fine particulate matter (PM2.5) and ozone, associated with Alzheimer’s disease (AD) risk. Mexico City (MC) children exhibit systemic and brain inflammation, low cerebrospinal fluid (CSF) Aβ1-42, breakdown of nasal, olfactory, alveolar-capillary, duodenal, and blood-brain barriers, volumetric and metabolic brain changes, attention and short-term memory deficits, and hallmarks of AD and Parkinson’s disease. Airborne iron-rich strongly magnetic combustion-derived nanoparticles (CDNPs) are present in young urbanites’ brains. Using transmission electron microscopy, we documented CDNPs in neurons, glia, choroid plexus, and neurovascular units of young MC residents versus matched clean air controls. CDNPs are associated with pathology in mitochondria, endoplasmic reticulum (ER), mitochondria-ER contacts (MERCs), axons,and dendrites. There is a significant difference in size and numbers between spherical CDNPs (>85%) and the angular, euhedral endogenous NPs (<15%). Spherical CDNPs (dogs 21.2 ± 7.1 nm in diameter versus humans 29.1 ± 11.2 nm, p = 0.002) are present in neurons, glia, choroid plexus, endothelium, nasal and olfactory epithelium, and in CSF at significantly higher in numbers in MC residents (p < 0.0001). Degenerated MERCs, abnormal mitochondria, and dilated ER are widespread, and CDNPs in close contact with neurofilaments, glial fibers, and chromatin are a potential source for altered microtubule dynamics, mitochondrial dysfunction, accumulation and aggregation of unfolded proteins, abnormal endosomal systems, altered insulin signaling, calcium homeostasis, apoptotic signaling, autophagy, and epigenetic changes. Highly oxidative, ubiquitous CDNPs constitute a novel path into AD pathogenesis. Exposed children and young adults need early neuroprotection and multidisciplinary prevention efforts to modify the course of AD at early stages.

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