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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
Calderón-Garcidueñas L, Gónzalez-Maciel A, Reynoso-Robles R, Delgado-Chávez R, Mukherjee PS, Kulesza RJ, Torres-Jardón R, Ávila-Ramírez J et al.. Environmental research, 2018-03-26
Topic: Air pollution and environmental exposures
Exposures to fine particulate matter (PM 2.5 ) and ozone (O 3 ) above USEPA standards are associated with Alzheimer's disease (AD) risk. Metropolitan Mexico City (MMC) residents have life time exposures to PM 2.5 and O 3 above USEPA standards. We investigated AD intra and extracellular protein aggregates and ultrastructural neurovascular pathology in 203 MMC residents age 25.36 ± 9.23 y. Immunohistochemical methods were used to identify AT8 hyperphosphorilated tau (Htau) and 4G8 (amyloid β 17-24). Primary outcomes: staging of Htau and amyloid, per decade and cumulative PM 2.5 (CPM 2.5 ) above standard. Apolipoprotein E allele 4 (APOE4), age and cause of death were secondary outcomes. Subcortical pretangle stage b was identified in an 11month old baby. Cortical tau pre-tangles, neurofibrillary tangles (NFT) Stages I-II, amyloid phases 1-2, Htau in substantia nigrae, auditory, oculomotor, trigeminal and autonomic systems were identified by the 2nd decade. Progression to NFT stages III-V was present in 24.8% of 30-40 y old subjects. APOE4 carriers have 4.92 times higher suicide odds (p = 0.0006), and 23.6 times higher odds of NFT V (p < 0.0001) v APOE4 non-carriers having similar CPM 2.5 exposure and age. Age (p = 0.0062) and CPM 2.5 (p = 0.0178) were significant for developing NFT V. Combustion-derived nanoparticles were associated with early and progressive damage to the neurovascular unit. Alzheimer's disease starting in the brainstem of young children and affecting 99.5% of young urbanites is a serious health crisis. Air pollution control should be prioritised. Childhood relentless Htau makes a fundamental target for neuroprotective interventions and the first two decades are critical. We recommend the concept of preclinical AD be revised and emphasize the need to define paediatric environmental, nutritional, metabolic and genetic risk factor interactions of paramount importance to prevent AD. AD evolving from childhood is threating the wellbeing of our children and future generations.
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APA 7th
Calderón-Garcidueñas, L., Gónzalez-Maciel, A., Reynoso-Robles, R., Delgado-Chávez, R., Mukherjee, P. S., Kulesza, R. J., et al. (2018). 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. Environmental research. https://doi.org/10.1016/j.envres.2018.03.023
Vancouver
Calderón-Garcidueñas L, Gónzalez-Maciel A, Reynoso-Robles R, Delgado-Chávez R, Mukherjee PS, Kulesza RJ, et al. 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. Environmental research. 2018. doi:10.1016/j.envres.2018.03.023. PMID: 29587223.
BibTeX
@article{calderongarciduenas2018-29587223,
author = {Calderón-Garcidueñas, L. and Gónzalez-Maciel, A. and Reynoso-Robles, R. and Delgado-Chávez, R. and Mukherjee, P. S. and Kulesza, R. J. and Torres-Jardón, R. and Ávila-Ramírez, J. and others},
title = {{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}},
journal = {Environmental research},
year = {2018},
doi = {10.1016/j.envres.2018.03.023},
pmid = {29587223},
url = {https://doi.org/10.1016/j.envres.2018.03.023}
}
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Key findings
- Exposures to fine particulate matter (PM 2.5 ) and ozone (O 3 ) above USEPA standards are associated with Alzheimer's disease (AD) risk.
- APOE4 carriers have 4.92 times higher suicide odds (p = 0.0006), and 23.6 times higher odds of NFT V (p < 0.0001) v APOE4 non-carriers having similar CPM 2.5 exposure and age.
- Age (p = 0.0062) and CPM 2.5 (p = 0.0178) were significant for developing NFT V.
- Combustion-derived nanoparticles were associated with early and progressive damage to the neurovascular unit.
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Study details
- Effect size24.8%; 99.5%
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 24 of the 58 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Environmental research) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2018 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29587223) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 24 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 24 of the 58 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | — |
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