Hallmarks of Alzheimer disease are evolving relentlessly in Metropolitan Mexico City infants, children and young adults. APOE4 carriers have higher suicide risk and higher odds of reaching NFT stage V at ≤ 40 years of age.
Level 4 - case-series / case-control
Cross-sectional post-mortem autopsy series without an unexposed control group
PubMed 29587223 · doi:10.1016/j.envres.2018.03.023
What was done
Post-mortem brain tissue was analyzed from 203 Metropolitan Mexico City residents (mean age 25.36 ± 9.23 years) chronically exposed to PM2.5 and ozone exceeding US EPA standards. Immunohistochemistry (AT8 for hyperphosphorylated tau and 4G8 for amyloid-beta 17-24) and electron microscopy were used to evaluate neurovascular damage and Alzheimer disease protein aggregates. Primary outcomes were the staging of hyperphosphorylated tau and amyloid-beta by decade and cumulative PM2.5 exposure above standard; secondary outcomes were APOE4 status, age, and cause of death.
What was found
Subcortical pretangle stage b was identified in an 11-month-old infant. Cortical tau pretangles, neurofibrillary tangle (NFT) stages I-II, amyloid phases 1-2, and hyperphosphorylated tau in substantia nigrae and autonomic systems appeared by the second decade. Progression to NFT stages III-V was present in 24.8% of individuals aged 30-40 years. APOE4 carriers had 4.92 times higher suicide odds (p = 0.0006) and 23.6 times higher odds of NFT stage V (p < 0.0001) compared with non-carriers having similar cumulative PM2.5 exposure and age. Age (p = 0.0062) and cumulative PM2.5 (p = 0.0178) were significant predictors for developing NFT stage V.
Why it matters
The findings indicate that Alzheimer disease neuropathological hallmarks can emerge in infancy and early adulthood among residents of highly polluted urban areas, with substantially elevated risk in APOE4 carriers.
Limits
The study is a descriptive autopsy series from a single metropolitan region lacking an unexposed or clean-air control group. The forensic sample is susceptible to selection bias. Air pollution exposure was estimated cumulatively rather than measured individually, and the abstract omits confidence intervals and adjustment for potential socioeconomic or metabolic confounders.
Cited by
- partial Postmortem analyses of infants in Mexico City found amyloid plaques in their brains.