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

Abstract

Exposures to fine particulate matter (PM 2.5 ) and ozone (O 3 ) ≥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 PM 2.5 and O 3 , 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 4 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 PM 2.5 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.

Gait and balance disturbances are common in young urbanites and associated with cognitive impairment. Air pollution and the historical development of Alzheimer's disease in the young

“… 69 We have described the presence of magnetite nanoparticles (NPs) in frontal cortex and hearts of MMC subjects often associated with other non-endogenous metals (including platinum, cadmium, cerium). 70 , 71 Indeed, NPs 72 are abundant in MMC air and contain metals, including Fe, Pb or Zn. 73 Villahermosa residents exposed mainly to -PM 2.5 rich in PAHs emitted from the flaring of source gas and incineration of oil condensates from gas- and oil extraction activities and from uncontrolled biomass burning, are having the lowest Tinetti gait scores, while MMC residents, are worse in balance and are being exposed to primary and secondary PM 2.5 associated with heavy duty diesel vehicles and the photochemical activity of the region.…”

Neurodegeneration-Associated Proteins in Human Olfactory Neurons Collected by Nasal Brushing

“…In healthy individuals, protein misfolding may occur early in life, and chronic exposure to air pollutants might accelerate the protein aggregation. It has been also suggested that AD and PD pathology may occur in the olfactory bulbs as a result of inhalation of air pollutants (Calderón-Garcidueñas et al, 2019).…”

Phosphodiesterase Inhibitors for Alzheimer’s Disease: A Systematic Review of Clinical Trials and Epidemiology with a Mechanistic Rationale

“…Excessive axonal Ca 2+ influx induces Wallerian axonal degeneration, and excessive cytoplasmic Ca 2+ influx induces excitotoxicity [346][347][348][349]. Olfactory sensory neurons are exposed to multiple sporadic AD risk factors, including combustion-derived carbon nanoparticles and microbial toxins [350][351][352][353]. AD pathogenic factors spread between neurons trans-synaptically in extracellular vesicles, such as exosomes [354][355][356][357][358], and tau pathology spreads through the brain in AD in a stereotypical fashion [2].…”

“…AD pathogenic factors spread between neurons trans-synaptically in extracellular vesicles, such as exosomes [354][355][356][357][358], and tau pathology spreads through the brain in AD in a stereotypical fashion [2]. Olfactory sensory neurons' axons project into the olfactory bulb [359], a brain region that is critically affected starting from the preclinical stages of AD [350,351]. Thus, PDE9A inhibition might promote pGC/cGMP-activated CNG-mediated Ca 2+ influx into olfactory sensory neurons, axon degeneration, excitotoxicity, and possibly propagation of AD pathologies to the olfactory bulb, possibly counterbalancing its positive effects and providing no net change in AD patients taking PDE9 inhibitors.…”