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.
Level 4 - case-series / case-control
Cross-sectional post-mortem case series
PubMed 29935448 · doi:10.1016/j.envres.2018.06.027
What was done
The researchers examined post-mortem olfactory bulb tissue from 179 deceased residents of Metropolitan Mexico City aged 11 months to 40 years. They assessed markers of Alzheimer's disease pathology (hyperphosphorylated tau [hTau], diffuse amyloid plaques, and vascular amyloid), Parkinson's disease pathology (Lewy neurites [LN] and alpha-synuclein aggregates), combustion-derived nanoparticles (CDNPs), and neurovascular unit damage. Pathological features were analyzed in relation to age, APOE genotype, and cause of death.
What was found
Hyperphosphorylated tau and Lewy neurites were detected in the olfactory bulbs of toddlers. In individuals in their second decade of life (n=57): - 84% (48/57) had hTau (mostly pretangle stages 1a and 1b in individuals ≤20 years). - 68% (39/57) had Lewy neurites and vascular amyloid. - 36% (21/57) had diffuse amyloid plaques. Endothelial phagocytosis of red blood cell fragments containing CDNPs and neurovascular unit damage were associated with axonal injury. APOE4 versus APOE3 carriers were 6 to 13 times more likely to exhibit olfactory bulb vascular amyloid, neuronal amyloid accumulation, alpha-synuclein aggregates, hTau neurofibrillary tangles, and neurites. In addition, APOE4 carriers were 4.57 times more likely than non-carriers to die by suicide.
Why it matters
This study provides histopathological evidence that hallmark neuropathological changes of Alzheimer's and Parkinson's diseases can emerge in the olfactory bulbs during childhood and adolescence in high-pollution urban settings, particularly among APOE4 carriers.
Limits
The study is a post-mortem observational series, and the abstract reports no low-pollution control cohort for direct baseline comparison. Individual-level air pollution exposure data are not detailed in the abstract. Autopsy cohorts carry inherent selection bias, and the cross-sectional post-mortem design cannot establish direct causality between particulate exposure and specific neuropathological outcomes.
Cited by
- partial Postmortem analyses of infants in Mexico City found amyloid plaques in their brains.