Alzheimer’s Disease and Alpha-Synuclein Neuropathology in the Olfactory Bulbs Of Children and Young Adults ≤40years Exposed to High Levels of Fine Particulate Matter Air Pollution in Metropolitan Mexico City: APOE4 Carriers at Higher Risk of Suicide Accelerate Their Olfactory Bulb Damage
There is growing evidence that air pollution is a risk factor for a number of neurodegenerative diseases, most notably Alzheimer’s (AD) and Parkinson’s (PD). It is generally assumed that the pathology of these diseases arises only later in life and commonly begins within olfactory eloquent pathways prior to the onset of the classical clinical symptoms. The present study demonstrates that chronic exposure to high levels of air pollution results in AD- and PD-related pathology within the olfactory bulbs of children and relatively young adults ranging in age from 11 months to 40 years. The olfactory bulbs (OBs) of 179 residents of highly polluted Metropolitan Mexico City were evaluated for AD- and alpha-synuclein-related pathology. Even in toddlers, hyperphosphorilated tau (hTau) and Lewy neurites (LN) were identified in the olfactory bulbs. By the second decade, 86% of the bulbs exhibited hTau (50/57), 76% LNs (45/57), 77% vascular amyloid (44/57), and 60% (34/57) mild diffuse amyloid plaques. During the first two decades, OBs neurovasculature unit damage is associated with combustion-derived nanoparticles and myelinated and unmyelinated axonal damage was evident. OB hTau neurites were associated with pretangle stages 1a and 1b in subjects ≤20 years of age, strongly suggesting olfactory deficits could potentially be an early guide of AD hTau stages. Compared to noncarriers, APOE4 carriers were 6 to 13 times more likely to exhibit OB vascular amyloid, neuronal amyloid accumulation, alpha-synuclein aggregates, hTau neurofibrillary tangles, and neurites. Remarkably, within this data set the APOE4 carriers were 4.7 times more likely than non-carriers to have committed suicide. The present findings, along with previous evidence that over a third of clinically healthy teens and young residents from the targeted pollution areas exhibit low scores on an odor identification test, support the concept that olfactory testing may aid in identifying young persons at high risk for neurodegenerative disease. Neuroprotective interventions in air pollution exposed individuals in the first two decades are critical. Air pollution control should be prioritized.
This is an author-produced, peer-reviewed version of this article. © 2018, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 license. The final, definitive version of this document can be found online at Environmental Research, doi: 10.1016/j.envres.2018.06.027
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Mukherjee, Partha S. (2018). "Alzheimer’s Disease and Alpha-Synuclein Neuropathology in the Olfactory Bulbs Of Children and Young Adults ≤40years Exposed to High Levels of Fine Particulate Matter Air Pollution in Metropolitan Mexico City: APOE4 Carriers at Higher Risk of Suicide Accelerate Their Olfactory Bulb Damage". Environmental Research, 166, 348-362. http://dx.doi.org/10.1016/j.envres.2018.06.027