Combustion-derived nanoparticles in key brain target cells and organelles in young urbanites: Culprit hidden in plain sight in Alzheimer's disease development

Angélica González-Maciel, Rafael Reynoso-Robles, Ricardo Torres-Jardón, Partha S. Mukherjee, Lilian Calderón-Garciduẽnas

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


Millions of children and young adults are exposed to fine particulate matter (PM2.5) and ozone, associated with Alzheimer's disease (AD) risk. Mexico City (MC) children exhibit systemic and brain inflammation, low cerebrospinal fluid (CSF)Aβ1-42, breakdown of nasal, olfactory, alveolar-capillary, duodenal, and blood-brain barriers, volumetric and metabolic brain changes, attention and short-term memory deficits, and hallmarks of AD and Parkinson's disease. Airborne iron-rich strongly magnetic combustion-derived nanoparticles (CDNPs) are present in young urbanites' brains. Using transmission electron microscopy, we documented CDNPs in neurons, glia, choroid plexus, and neurovascular units of youngMCresidents versus matched clean air controls. CDNPs are associated with pathology in mitochondria, endoplasmic reticulum (ER), mitochondria-ER contacts (MERCs), axons, and dendrites. There is a significant difference in size and numbers between spherical CDNPs (>85%) and the angular, euhedral endogenous NPs (<15%). Spherical CDNPs (dogs 21.2±7.1 nm in diameter versus humans 29.1±11.2 nm, p = 0.002) are present in neurons, glia, choroid plexus, endothelium, nasal and olfactory epithelium, and in CSF at significantly higher in numbers in MC residents (p < 0.0001). Degenerated MERCs, abnormal mitochondria, and dilated ER are widespread, and CDNPs in close contact with neurofilaments, glial fibers, and chromatin are a potential source for altered microtubule dynamics, mitochondrial dysfunction, accumulation and aggregation of unfolded proteins, abnormal endosomal systems, altered insulin signaling, calcium homeostasis, apoptotic signaling, autophagy, and epigenetic changes. Highly oxidative, ubiquitous CDNPs constitute a novel path into AD pathogenesis. Exposed children and young adults need early neuroprotection and multidisciplinary prevention efforts to modify the course of AD at early stages.

Original languageEnglish
Title of host publicationAlzheimer's Disease and Air Pollution
Subtitle of host publicationThe Development and Progression of a Fatal Disease from Childhood and the Opportunities for Early Prevention
PublisherIOS Press
Number of pages20
ISBN (Electronic)9781643681597
ISBN (Print)9781643681580
StatePublished - May 3 2021


  • Air pollution
  • Alzheimer's disease
  • Brain damage
  • Children
  • Electron microscopy
  • Epigenetics
  • Magnetite
  • Mexico city
  • Mitochondria-ER contacts
  • Nanoparticles
  • Oxidative damage
  • Ultrafine particulate matter


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