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Culprit Hidden in Plain Sight in Alzheimer’s Development

Summary: Study raises further concern about exposure to air pollution and Alzheimer’s development.

Source: IOS Press.

Combustion-derived nanoparticles in key brain target cells and organelles in young urbanites.

A new study by researchers at the University of Montana, Universidad del Valle de México, Instituto Nacional de Pediatría, Boise State, and Universidad Nacional Autónoma de México, heightens concerns over the detrimental short- and long-term impact of airborne iron-rich strongly magnetic combustion-derived nanoparticles (CDNPs) present in young urbanites’ brains. Using transmission electron microscopy, the researchers documented by abundant combustion nanoparticles in neurons, glial cells, choroid plexus, and neurovascular units of Mexico City children, teens and young adults chronically exposed to concentrations above the US-EPA standards for fine particulate matter. Residents in Mexico City are exposed from conception to harmful neurotoxic air pollutants. These findings are published in the Journal of Alzheimer’s Disease.

The detrimental impact of these tiny particles getting into the brain through the nasal and olfactory epithelium, the lungs and the gastrointestinal system is quickly recognized by extensive alterations in critical neuronal organelles including mitochondria, as well as axons and dendrites. Since these nanoparticles are in close contact with neurofilaments, glial fibers and chromatin, the researchers are very concerned about their potential for altering microtubule dynamics, accumulation and aggregation of unfolded proteins, mitochondrial dysfunction, altered calcium homeostasis and insulin signaling, and epigenetic changes.

Mexico City children, teens and young adults have shown key markers of Alzheimer’s disease (AD): hyperphosphorylated tau and amyloid plaques along with significant brain and intrathecal neuroinflammation, dysregulated immune responses, breakdown of epithelial and endothelial barriers, extensive damage to the neurovascular unit, and brain accumulation of metals associated with combustion. Moreover, these seemingly healthy young people have olfaction deficits, dysregulation of feeding hormones, deficiencies in attention and short-term memory, and below-average scores in Verbal and Full Scale IQ compared to age, gender, and socioeconomic status-matched low air pollution residents. The cognitive problem is particularly serious for overweight female teens carrying an allele of the apolipoprotein E (APOE) ε4, the most prevalent genetic risk factor for AD.

“In the context of serious continuous exposures to high concentrations of fine particulate matter (PM 2.5) and ozone, our current electron microscopy findings and the extensive literature associating air pollutants with brain damage, the issue of who is at risk of neurodegeneration at an early age should be an urgent public health concern,” said Dr. Lilian Calderon-Garcidueňas. “The effects of poverty, urban violence and urban stress on impaired cognitive skills are also very important for the developing brain and can’t be ignored. We know gender, BMI, and APOE influence children’s cognitive responses to air pollution.”

According to the researchers, the problem of having combustion-derived nanoparticles in children’s brains — developing brains — is very serious. These particles are ubiquitous and present in high concentrations in children as young as 3 years old. The particles contain transition neurotoxic metals and they are certainly causing extensive brain damage in key organelles. “The predominant combustion particles in young brains have properties that enable them to cause oxidative damage because these nanoparticles are capable of crossing all barriers. No barrier is spared,” Dr. Calderón-Garcidueňas emphasized.

Angélica González-Maciel added, “People with children and teens struggling in school and facing a significant increase of violence in school, streets, parks, and public transportation are deeply concerned about the impact these particles have on children’s behavioral patterns and academic performance and parents question what they can do to protect their families”.

All involved researchers agreed that in spite of the driving restrictions policies [that are clearly ineffective (Davis LW. Sci Rep 7: 41652, 2017)], millions of Mexico City residents continue to be exposed to very unhealthy concentrations of both PM 2.5 and ozone, both known risk factors for AD.

“Our results,” said Dr. Calderón-Garcidueňas, “highlight the urgent need for significantly decreasing the concentrations of fine particulate matter and ozone in Mexico City and the adjacent polluted states. Multidisciplinary intervention strategies could provide paths for prevention or amelioration of air pollution targeted cognitive deficits and possible long-term AD progression.”

Image shows brain slices.

This is an exposure chamber in Mexico. NeuroscienceNews.com image is credited to Dr. Lilian Calderone.

The combined effects of combustion-derived nanoparticles, residency in a highly-polluted city, poor nutrition, obesity, metabolic syndrome, urban stress, lower brain and cognitive reserves, and APOE ε4 could lead to an acceleration of neurodegenerative changes among precarious young brains.

The authors concluded: highly oxidative, combustion nanoparticles entering young developing brains — the culprit hidden in plain sight in Alzheimer’s disease development — constitute a very serious public health issue, with grave social and economic consequences.

Efforts should also be aimed to identify and neuroprotect high risk young populations. Unfortunately, to date that is not happening.

About this neuroscience research article

Source: Lilian Calderon-Garcidueňas – IOS Press
Image Source: NeuroscienceNews.com image is credited to Dr. Lilian Calderone.
Original Research: Abstract for “Apolipoprotein E4, Gender, Body Mass Index, Inflammation, Insulin Resistance, and Air Pollution Interactions: Recipe for Alzheimer’s Disease Development in Mexico City Young Females” by Calderón-Garcidueñas, Lilian and de la Monte, Suzanne M. in Journal of Alzheimer’s Disease. Published online July 8 2017 doi:10.3233/JAD-161299

Cite This NeuroscienceNews.com Article
IOS Press “Culprit Hidden in Plain Sight in Alzheimer’s Development.” NeuroscienceNews. NeuroscienceNews, 8 June 2017.
<http://neurosciencenews.com/fine-particulate-alzheimers-6871/>.
IOS Press (2017, June 8). Culprit Hidden in Plain Sight in Alzheimer’s Development. NeuroscienceNew. Retrieved June 8, 2017 from http://neurosciencenews.com/fine-particulate-alzheimers-6871/
IOS Press “Culprit Hidden in Plain Sight in Alzheimer’s Development.” http://neurosciencenews.com/fine-particulate-alzheimers-6871/ (accessed June 8, 2017).

Abstract

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

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.

“Apolipoprotein E4, Gender, Body Mass Index, Inflammation, Insulin Resistance, and Air Pollution Interactions: Recipe for Alzheimer’s Disease Development in Mexico City Young Females” by Calderón-Garcidueñas, Lilian and de la Monte, Suzanne M. in Journal of Alzheimer’s Disease. Published online July 8 2017 doi:10.3233/JAD-161299

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