skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

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

Journal Article · · Environmental Research
 [1]; ;  [2];  [3];  [4];  [5];  [6];  [7]
  1. The University of Montana, Missoula, MT, 59812 (United States)
  2. Instituto Nacional de Pediatría, Mexico City, 04530 (Mexico)
  3. Auditory Research Center, Lake Erie College of Osteopathic Medicine, Erie, PA 16509 (United States)
  4. Mathematics Department, Boise State University, Boise, ID 83725 (United States)
  5. Centro de Ciencias de la Atmósfera, Universidad Nacional Autónoma de México, 04310 (Mexico)
  6. Aerosol Physics, Faculty of Natural Sciences, Tampere University of Technology, FI-33101 Tampere (Finland)
  7. Smell and Taste Center, Department of Otorhinolaryngology: Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, 19104 (United States)

Highlights: • Air pollution targets olfactory bulbs in young city dwellers. • Olfactory bulb hyperphosphorylated tau and Lewy neurites are present in Mexico City toddlers. • APOE4 carriers accelerate their OB pathology and have 4.7 times higher suicide odds v APOE3. • Olfactory testing may aid in identifying young persons at high risk for neurodegenerative disease. • Early neuroprotective interventions in PM{sub 2.5} and CDNP's exposed individuals ≤ 20 years are critical. 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 (PM{sub 2.5}) and CDNP's exposed individuals ≤ 20 years of age, and the critical need for air pollution control.

OSTI ID:
23107938
Journal Information:
Environmental Research, Vol. 166; Other Information: Copyright (c) 2018 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0013-9351
Country of Publication:
United States
Language:
English