APOE Peripheral and Brain Impact: APOE4 Carriers Accelerate Their Alzheimer Continuum and Have a High Risk of Suicide in PM<sub>2.5</sub> Polluted Cities
This Review emphasizes the impact of APOE4—the most significant genetic risk factor for Alzheimer’s disease (AD)—on peripheral and neural effects starting in childhood. We discuss major mechanistic players associated with the APOE alleles’ effects in humans to understand their impact from conception...
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| Format: | Article |
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MDPI AG
2023-05-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/6/927 |
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| author | Lilian Calderón-Garcidueñas Jacqueline Hernández-Luna Mario Aiello-Mora Rafael Brito-Aguilar Pablo A. Evelson Rodolfo Villarreal-Ríos Ricardo Torres-Jardón Alberto Ayala Partha S. Mukherjee |
| author_facet | Lilian Calderón-Garcidueñas Jacqueline Hernández-Luna Mario Aiello-Mora Rafael Brito-Aguilar Pablo A. Evelson Rodolfo Villarreal-Ríos Ricardo Torres-Jardón Alberto Ayala Partha S. Mukherjee |
| author_sort | Lilian Calderón-Garcidueñas |
| collection | DOAJ |
| description | This Review emphasizes the impact of APOE4—the most significant genetic risk factor for Alzheimer’s disease (AD)—on peripheral and neural effects starting in childhood. We discuss major mechanistic players associated with the APOE alleles’ effects in humans to understand their impact from conception through all life stages and the importance of detrimental, synergistic environmental exposures. APOE4 influences AD pathogenesis, and exposure to fine particulate matter (PM<sub>2.5</sub>), manufactured nanoparticles (NPs), and ultrafine particles (UFPs) associated with combustion and friction processes appear to be major contributors to cerebrovascular dysfunction, neuroinflammation, and oxidative stress. In the context of outdoor and indoor PM pollution burden—as well as Fe, Ti, and Al alloys; Hg, Cu, Ca, Sn, and Si UFPs/NPs—in placenta and fetal brain tissues, urban APOE3 and APOE4 carriers are developing AD biological disease hallmarks (hyperphosphorylated-tau (P-tau) and amyloid beta 42 plaques (Aβ<sub>42</sub>)). Strikingly, for Metropolitan Mexico City (MMC) young residents ≤ 40 y, APOE4 carriers have 4.92 times higher suicide odds and 23.6 times higher odds of reaching Braak NFT V stage versus APOE4 non-carriers. The National Institute on Aging and Alzheimer’s Association (NIA-AA) framework could serve to test the hypothesis that UFPs and NPs are key players for oxidative stress, neuroinflammation, protein aggregation and misfolding, faulty complex protein quality control, and early damage to cell membranes and organelles of neural and vascular cells. Noninvasive biomarkers indicative of the P-tau and Aβ<sub>42</sub> abnormal protein deposits are needed across the disease continuum starting in childhood. Among the 21.8 million MMC residents, we have potentially 4 million APOE4 carriers at accelerated AD progression. These APOE4 individuals are prime candidates for early neuroprotective interventional trials. APOE4 is key in the development of AD evolving from childhood in highly polluted urban centers dominated by anthropogenic and industrial sources of pollution. APOE4 subjects are at higher early risk of AD development, and neuroprotection ought to be implemented. Effective reductions of PM<sub>2.5</sub>, UFP, and NP emissions from all sources are urgently needed. Alzheimer’s Disease prevention ought to be at the core of the public health response and physicians-scientist minority research be supported. |
| first_indexed | 2024-03-11T02:42:19Z |
| format | Article |
| id | doaj.art-ee1929167fae47d3b4f00fc828d5315c |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-11T02:42:19Z |
| publishDate | 2023-05-01 |
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| series | Biomolecules |
| spelling | doaj.art-ee1929167fae47d3b4f00fc828d5315c2023-11-18T09:30:45ZengMDPI AGBiomolecules2218-273X2023-05-0113692710.3390/biom13060927APOE Peripheral and Brain Impact: APOE4 Carriers Accelerate Their Alzheimer Continuum and Have a High Risk of Suicide in PM<sub>2.5</sub> Polluted CitiesLilian Calderón-Garcidueñas0Jacqueline Hernández-Luna1Mario Aiello-Mora2Rafael Brito-Aguilar3Pablo A. Evelson4Rodolfo Villarreal-Ríos5Ricardo Torres-Jardón6Alberto Ayala7Partha S. Mukherjee8College of Health, The University of Montana, Missoula, MT 59812, USARadiology Department, HMG, Mexico City 04380, MexicoOtorrinolaryngology Department, Instituto Nacional de Cardiología, Mexico City 14080, MexicoUniversidad del Valle de México, Mexico City 14370, MexicoFacultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires C1113 AAD, ArgentinaUniversidad Autónoma de Piedras Negras, Piedras Negras 26000, MexicoInstituto de Ciencias de la Atmósfera y Cambio Climático, Universidad Nacional Autónoma de México, Mexico City 04510, MexicoSacramento Metropolitan Air Quality Management District, Sacramento, CA 95814, USAInterdisciplinary Statistical Research Unit, Indian Statistical Institute, Kolkata 700108, IndiaThis Review emphasizes the impact of APOE4—the most significant genetic risk factor for Alzheimer’s disease (AD)—on peripheral and neural effects starting in childhood. We discuss major mechanistic players associated with the APOE alleles’ effects in humans to understand their impact from conception through all life stages and the importance of detrimental, synergistic environmental exposures. APOE4 influences AD pathogenesis, and exposure to fine particulate matter (PM<sub>2.5</sub>), manufactured nanoparticles (NPs), and ultrafine particles (UFPs) associated with combustion and friction processes appear to be major contributors to cerebrovascular dysfunction, neuroinflammation, and oxidative stress. In the context of outdoor and indoor PM pollution burden—as well as Fe, Ti, and Al alloys; Hg, Cu, Ca, Sn, and Si UFPs/NPs—in placenta and fetal brain tissues, urban APOE3 and APOE4 carriers are developing AD biological disease hallmarks (hyperphosphorylated-tau (P-tau) and amyloid beta 42 plaques (Aβ<sub>42</sub>)). Strikingly, for Metropolitan Mexico City (MMC) young residents ≤ 40 y, APOE4 carriers have 4.92 times higher suicide odds and 23.6 times higher odds of reaching Braak NFT V stage versus APOE4 non-carriers. The National Institute on Aging and Alzheimer’s Association (NIA-AA) framework could serve to test the hypothesis that UFPs and NPs are key players for oxidative stress, neuroinflammation, protein aggregation and misfolding, faulty complex protein quality control, and early damage to cell membranes and organelles of neural and vascular cells. Noninvasive biomarkers indicative of the P-tau and Aβ<sub>42</sub> abnormal protein deposits are needed across the disease continuum starting in childhood. Among the 21.8 million MMC residents, we have potentially 4 million APOE4 carriers at accelerated AD progression. These APOE4 individuals are prime candidates for early neuroprotective interventional trials. APOE4 is key in the development of AD evolving from childhood in highly polluted urban centers dominated by anthropogenic and industrial sources of pollution. APOE4 subjects are at higher early risk of AD development, and neuroprotection ought to be implemented. Effective reductions of PM<sub>2.5</sub>, UFP, and NP emissions from all sources are urgently needed. Alzheimer’s Disease prevention ought to be at the core of the public health response and physicians-scientist minority research be supported.https://www.mdpi.com/2218-273X/13/6/927air pollutionchildrenAlzheimerAPOE4early biomarkersamyloid beta |
| spellingShingle | Lilian Calderón-Garcidueñas Jacqueline Hernández-Luna Mario Aiello-Mora Rafael Brito-Aguilar Pablo A. Evelson Rodolfo Villarreal-Ríos Ricardo Torres-Jardón Alberto Ayala Partha S. Mukherjee APOE Peripheral and Brain Impact: APOE4 Carriers Accelerate Their Alzheimer Continuum and Have a High Risk of Suicide in PM<sub>2.5</sub> Polluted Cities Biomolecules air pollution children Alzheimer APOE4 early biomarkers amyloid beta |
| title | APOE Peripheral and Brain Impact: APOE4 Carriers Accelerate Their Alzheimer Continuum and Have a High Risk of Suicide in PM<sub>2.5</sub> Polluted Cities |
| title_full | APOE Peripheral and Brain Impact: APOE4 Carriers Accelerate Their Alzheimer Continuum and Have a High Risk of Suicide in PM<sub>2.5</sub> Polluted Cities |
| title_fullStr | APOE Peripheral and Brain Impact: APOE4 Carriers Accelerate Their Alzheimer Continuum and Have a High Risk of Suicide in PM<sub>2.5</sub> Polluted Cities |
| title_full_unstemmed | APOE Peripheral and Brain Impact: APOE4 Carriers Accelerate Their Alzheimer Continuum and Have a High Risk of Suicide in PM<sub>2.5</sub> Polluted Cities |
| title_short | APOE Peripheral and Brain Impact: APOE4 Carriers Accelerate Their Alzheimer Continuum and Have a High Risk of Suicide in PM<sub>2.5</sub> Polluted Cities |
| title_sort | apoe peripheral and brain impact apoe4 carriers accelerate their alzheimer continuum and have a high risk of suicide in pm sub 2 5 sub polluted cities |
| topic | air pollution children Alzheimer APOE4 early biomarkers amyloid beta |
| url | https://www.mdpi.com/2218-273X/13/6/927 |
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