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Alzheimer's disease and alpha-synuclein pathology in the olfactory bulbs of infants, children, teens and adults ≤ 40 years in Metropolitan Mexico City. APOE4 carriers at higher risk of suicide accelerate their olfactory bulb pathology

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Alzheimer's disease and alpha-synuclein pathology in the olfactory bulbs of infants, children, teens and adults ≤ 40 years in Metropolitan Mexico City. APOE4 carriers at higher risk of suicide accelerate their olfactory bulb pathology. / Calderón-Garcidueñas, Lilian; González-Maciel, Angélica; Reynoso-Robles, Rafael; Kulesza, Randy J.; Mukherjee, Partha S.; Torres-Jardón, Ricardo; Rönkkö, Topi; Doty, Richard L.

In: Environmental Research, Vol. 166, 01.10.2018, p. 348-362.

Research output: Contribution to journalArticleScientificpeer-review

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Calderón-Garcidueñas, L., González-Maciel, A., Reynoso-Robles, R., Kulesza, R. J., Mukherjee, P. S., Torres-Jardón, R., ... Doty, R. L. (2018). Alzheimer's disease and alpha-synuclein pathology in the olfactory bulbs of infants, children, teens and adults ≤ 40 years in Metropolitan Mexico City. APOE4 carriers at higher risk of suicide accelerate their olfactory bulb pathology. Environmental Research, 166, 348-362. https://doi.org/10.1016/j.envres.2018.06.027

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Calderón-Garcidueñas, Lilian ; González-Maciel, Angélica ; Reynoso-Robles, Rafael ; Kulesza, Randy J. ; Mukherjee, Partha S. ; Torres-Jardón, Ricardo ; Rönkkö, Topi ; Doty, Richard L. / Alzheimer's disease and alpha-synuclein pathology in the olfactory bulbs of infants, children, teens and adults ≤ 40 years in Metropolitan Mexico City. APOE4 carriers at higher risk of suicide accelerate their olfactory bulb pathology. In: Environmental Research. 2018 ; Vol. 166. pp. 348-362.

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@article{6a06317f86724d8e871422e09b3ae1f7,
title = "Alzheimer's disease and alpha-synuclein pathology in the olfactory bulbs of infants, children, teens and adults ≤ 40 years in Metropolitan Mexico City. APOE4 carriers at higher risk of suicide accelerate their olfactory bulb pathology",
abstract = "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 ages 11 months to 40 years. The olfactory bulbs (OBs) of 179 residents of highly polluted Metropolitan Mexico City (MMC) were evaluated for AD- and alpha-synuclein-related pathology. Even in toddlers, hyperphosphorylated tau (hTau) and Lewy neurites (LN) were identified in the OBs. By the second decade, 84{\%} of the bulbs exhibited hTau (48/57), 68{\%} LNs and vascular amyloid (39/57) and 36{\%} (21/57) diffuse amyloid plaques. OB active endothelial phagocytosis of red blood cell fragments containing combustion-derived nanoparticles (CDNPs) and the neurovascular unit damage were associated with myelinated and unmyelinated axonal damage. OB hTau neurites were associated mostly with pretangle stages 1a and 1b in subjects ≤ 20 years of age, strongly suggesting olfactory deficits could potentially be an early guide of AD pretangle subcortical and cortical hTau. APOE4 versus APOE3 carriers were 6–13 times more likely to exhibit OB vascular amyloid, neuronal amyloid accumulation, alpha-synuclein aggregates, hTau neurofibrillary tangles, and neurites. Remarkably, APOE4 carriers were 4.57 times more likely than non-carriers to die by suicide. The present findings, along with previous data that over a third of clinically healthy MMC teens and young adults exhibit low scores on an odor identification test, support the concept that olfactory testing may aid in identifying young people at high risk for neurodegenerative diseases. Moreover, results strongly support early neuroprotective interventions in fine particulate matter (PM2.5) and CDNP's exposed individuals ≤ 20 years of age, and the critical need for air pollution control.",
keywords = "Air pollution, Alpha synuclein, Alpha-synucleinopathies, Alzheimer, Amyloid plaques, APOE4, Children, Combustion-derived nanoparticles CDNPs, Corpora amylacea, Hyperphosphorylated tau, Mexico City, Nanocluster aerosol particles, Olfactory bulb, Parkinson, PM, Suicide, Tauopathies, Young adults",
author = "Lilian Calder{\'o}n-Garcidue{\~n}as and Ang{\'e}lica Gonz{\'a}lez-Maciel and Rafael Reynoso-Robles and Kulesza, {Randy J.} and Mukherjee, {Partha S.} and Ricardo Torres-Jard{\'o}n and Topi R{\"o}nkk{\"o} and Doty, {Richard L.}",
year = "2018",
month = "10",
day = "1",
doi = "10.1016/j.envres.2018.06.027",
language = "English",
volume = "166",
pages = "348--362",
journal = "Environmental Research",
issn = "0013-9351",
publisher = "Elsevier",

}

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TY - JOUR

T1 - Alzheimer's disease and alpha-synuclein pathology in the olfactory bulbs of infants, children, teens and adults ≤ 40 years in Metropolitan Mexico City. APOE4 carriers at higher risk of suicide accelerate their olfactory bulb pathology

AU - Calderón-Garcidueñas, Lilian

AU - González-Maciel, Angélica

AU - Reynoso-Robles, Rafael

AU - Kulesza, Randy J.

AU - Mukherjee, Partha S.

AU - Torres-Jardón, Ricardo

AU - Rönkkö, Topi

AU - Doty, Richard L.

PY - 2018/10/1

Y1 - 2018/10/1

N2 - 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 ages 11 months to 40 years. The olfactory bulbs (OBs) of 179 residents of highly polluted Metropolitan Mexico City (MMC) were evaluated for AD- and alpha-synuclein-related pathology. Even in toddlers, hyperphosphorylated tau (hTau) and Lewy neurites (LN) were identified in the OBs. By the second decade, 84% of the bulbs exhibited hTau (48/57), 68% LNs and vascular amyloid (39/57) and 36% (21/57) diffuse amyloid plaques. OB active endothelial phagocytosis of red blood cell fragments containing combustion-derived nanoparticles (CDNPs) and the neurovascular unit damage were associated with myelinated and unmyelinated axonal damage. OB hTau neurites were associated mostly with pretangle stages 1a and 1b in subjects ≤ 20 years of age, strongly suggesting olfactory deficits could potentially be an early guide of AD pretangle subcortical and cortical hTau. APOE4 versus APOE3 carriers were 6–13 times more likely to exhibit OB vascular amyloid, neuronal amyloid accumulation, alpha-synuclein aggregates, hTau neurofibrillary tangles, and neurites. Remarkably, APOE4 carriers were 4.57 times more likely than non-carriers to die by suicide. The present findings, along with previous data that over a third of clinically healthy MMC teens and young adults exhibit low scores on an odor identification test, support the concept that olfactory testing may aid in identifying young people at high risk for neurodegenerative diseases. Moreover, results strongly support early neuroprotective interventions in fine particulate matter (PM2.5) and CDNP's exposed individuals ≤ 20 years of age, and the critical need for air pollution control.

AB - 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 ages 11 months to 40 years. The olfactory bulbs (OBs) of 179 residents of highly polluted Metropolitan Mexico City (MMC) were evaluated for AD- and alpha-synuclein-related pathology. Even in toddlers, hyperphosphorylated tau (hTau) and Lewy neurites (LN) were identified in the OBs. By the second decade, 84% of the bulbs exhibited hTau (48/57), 68% LNs and vascular amyloid (39/57) and 36% (21/57) diffuse amyloid plaques. OB active endothelial phagocytosis of red blood cell fragments containing combustion-derived nanoparticles (CDNPs) and the neurovascular unit damage were associated with myelinated and unmyelinated axonal damage. OB hTau neurites were associated mostly with pretangle stages 1a and 1b in subjects ≤ 20 years of age, strongly suggesting olfactory deficits could potentially be an early guide of AD pretangle subcortical and cortical hTau. APOE4 versus APOE3 carriers were 6–13 times more likely to exhibit OB vascular amyloid, neuronal amyloid accumulation, alpha-synuclein aggregates, hTau neurofibrillary tangles, and neurites. Remarkably, APOE4 carriers were 4.57 times more likely than non-carriers to die by suicide. The present findings, along with previous data that over a third of clinically healthy MMC teens and young adults exhibit low scores on an odor identification test, support the concept that olfactory testing may aid in identifying young people at high risk for neurodegenerative diseases. Moreover, results strongly support early neuroprotective interventions in fine particulate matter (PM2.5) and CDNP's exposed individuals ≤ 20 years of age, and the critical need for air pollution control.

KW - Air pollution

KW - Alpha synuclein

KW - Alpha-synucleinopathies

KW - Alzheimer

KW - Amyloid plaques

KW - APOE4

KW - Children

KW - Combustion-derived nanoparticles CDNPs

KW - Corpora amylacea

KW - Hyperphosphorylated tau

KW - Mexico City

KW - Nanocluster aerosol particles

KW - Olfactory bulb

KW - Parkinson

KW - PM

KW - Suicide

KW - Tauopathies

KW - Young adults

U2 - 10.1016/j.envres.2018.06.027

DO - 10.1016/j.envres.2018.06.027

M3 - Article

VL - 166

SP - 348

EP - 362

JO - Environmental Research

JF - Environmental Research

SN - 0013-9351

ER -