Mexico City (MC) children have lifetime exposures to concentrations of air pollutants above the current USA standards, including fine particulate matter (PM 2.5). Metropolitan Mexico City is an example of extreme urban growth and serious environmental pollution including high exposures to PM 2.5, ozone, polycyclic aromatic hydrocarbons (PAH), metals, endotoxins, tobacco smog, open waste dumps, highly polluting heavy duty trucks (not subjected to any pollution controls), etc., resulting in millions of children involuntarily exposed to harmful air neurotoxic substances every day since conception.
The results of this study including the significantly low concentrations of Aβ 1-42 and Brain-derived neurotrophic factor (BDNF) in MC children versus controls, suggests that major changes in key neural proteins playing major roles in neurotoxicity, cell survival, axonal and dendritic growth, and synaptic plasticity are evolving in urban MC children. Decreased levels of BDNF are associated with the development of obesity, depression, mood disorders, and neurodegeneration. Interestingly, Mexico City children increased their levels of total prion protein (TPrP) with cumulative PM2.5 up to 5 μg/m3 and then decreased, regardless of cumulative value or age. The low values of this key protein are likely detrimental given its protective effects against oxidative stress and its role in cell signaling, metal interactions, memory, myelin maintenance, axonal growth and neuronal development. Total synuclein showed an increment in childhood years related to cumulated PM2.5, followed by a decrease after age 12 years, while the abnormal synuclein associated with Parkinson’s disease exhibited a tendency to increase with cumulated PM2.5.
Mexico City children, teens, and young adults have shown a key marker of Alzheimer disease (AD): hyperphosphorylated tau along significant brain and intrathecal neuroinflammation, dysregulated immune responses, breakdown of epithelial and endothelial barriers, damage to the neurovascular unit, and brain accumulation of metals associated with combustion. Moreover, seemingly healthy children in Mexico City have olfaction deficits, dysregulation of feeding regulatory hormones, deficiencies in attention and short-term memory, and below-average scores in Verbal and Full Scale IQ compared to low air pollution children.
“Researchers are very concerned young Mexico City urbanites exhibit evidence of spectral markers of neurodegeneration that are often seen in adults with mild cognitive impairment, in Alzheimer patients and in mouse models of Alzheimer’s disease” said Dr. Lilian Calderón-Garcidueňas.
“Our concern about Parkinson’s disease is also increased when we observed children and teens with early autonomic dysfunction and in brainstem materials, extensive accumulation of α- synuclein in key nuclei including auditory nuclei and the dorsal nucleus of the vagus” said authors.
“These results add to growing data from our laboratory and others, suggesting urban residents with chronic high exposures to ozone and fine particulate matter have a higher risk for developing Alzheimer’s disease (Jung et al., J Alzheimers Dis, 44, 573-584, 2015) and the potential key role of environmental magnetite nanoparticles in the brains of Mexico City residents (Maher et al., Proc Natl Acad Sci U S A, early edition) commented Dr. Calderón-Garcidueňas.
Air pollution is a serious public health issue and exposures to concentrations of air pollutants at or above the current standards have been clearly linked to neuroinflammation and neurodegeneration.
There is an urgent need for studying air pollution interactions impacting children’s brains and their responses, which could provide new avenues for Alzheimer’s and Parkinson’s disease prevention.
The authors concluded: “We have a 50-year window of opportunity between the time urban children experience the detrimental effects we are describing here and when they will present with mild cognitive impairment, dementia, tremor or all of the above. Our efforts should be aimed to identify and mitigate environmental factors influencing the early development of neurodegenerative diseases and to neuroprotect high risk children. Unfortunately, to date there has been no support for studying the detrimental neurodegenerative effects of air pollution on the pediatric brain.”
# # #
Lilian Calderón-Garcidueňas, MA, MD, PhD
University of Montana
+1 406 243 4785
NOTES FOR EDITORS
“Cerebrospinal fluid biomarkers in highly exposed PM2.5 urbanites: The risk of Alzheimer’s and Parkinson’s diseases in young Mexico City residents” by Lilian Calderón-Garcidueňas, José Avila-Ramírez, Ana Calderón-Garcidueñas, Tonatiuh González-Heredia, Hilda Acuña-Ayala, Chih-kai Chao, Charles Thompson, Rubén Ruiz- Ramos, Victor Cortés-González, Luz Martínez-Martínez, Mario Alberto García-Pérez, Jacques Reis, Partha S. Mukherjee, Ricardo Torres-Jardón, Ingolf Lachmann, J Alzheimers Dis 54, 597-613, 2016.
ABOUT THE JOURNAL OF ALZHEIMER’S DISEASE (JAD)
The Journal of Alzheimer’s Disease is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment and psychology of Alzheimer’s disease. The journal publishes research reports, reviews, short communications, book reviews, and letters-to-the-editor. Published by IOS Press.