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APOE ε2 resilience for Alzheimer's disease is mediated by plasma lipid species: Analysis of three independent cohort studies
INTRODUCTION: The apolipoprotein E (APOE) genotype is the strongest genetic risk factor for late‐onset Alzheimer's disease. However, its effect on lipid metabolic pathways, and their mediating effect on disease risk, is poorly understood. METHODS: We performed lipidomic analysis on three indepe...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
John Wiley and Sons Inc.
2022
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9787288/ https://www.ncbi.nlm.nih.gov/pubmed/35077012 http://dx.doi.org/10.1002/alz.12538 |
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| author | Wang, Tingting Huynh, Kevin Giles, Corey Mellett, Natalie A Duong, Thy Nguyen, Anh Lim, Wei Ling Florence Smith, Alex AT Olshansky, Gavriel Cadby, Gemma Hung, Joseph Hui, Jennie Beilby, John Watts, Gerald F Chatterjee, Pratishtha Martins, Ian Laws, Simon M Bush, Ashley I Rowe, Christopher C Villemagne, Victor L Ames, David Masters, Colin L Taddei, Kevin Doré, Vincent Fripp, Jürgen Arnold, Matthias Kastenmüller, Gabi Nho, Kwangsik Saykin, Andrew J Baillie, Rebecca Han, Xianlin Martins, Ralph N Moses, Eric K Kaddurah‐Daouk, Rima Meikle, Peter J |
| author_facet | Wang, Tingting Huynh, Kevin Giles, Corey Mellett, Natalie A Duong, Thy Nguyen, Anh Lim, Wei Ling Florence Smith, Alex AT Olshansky, Gavriel Cadby, Gemma Hung, Joseph Hui, Jennie Beilby, John Watts, Gerald F Chatterjee, Pratishtha Martins, Ian Laws, Simon M Bush, Ashley I Rowe, Christopher C Villemagne, Victor L Ames, David Masters, Colin L Taddei, Kevin Doré, Vincent Fripp, Jürgen Arnold, Matthias Kastenmüller, Gabi Nho, Kwangsik Saykin, Andrew J Baillie, Rebecca Han, Xianlin Martins, Ralph N Moses, Eric K Kaddurah‐Daouk, Rima Meikle, Peter J |
| author_sort | Wang, Tingting |
| collection | PubMed |
| description | INTRODUCTION: The apolipoprotein E (APOE) genotype is the strongest genetic risk factor for late‐onset Alzheimer's disease. However, its effect on lipid metabolic pathways, and their mediating effect on disease risk, is poorly understood. METHODS: We performed lipidomic analysis on three independent cohorts (the Australian Imaging, Biomarkers and Lifestyle [AIBL] flagship study, n = 1087; the Alzheimer's Disease Neuroimaging Initiative [ADNI] 1 study, n = 819; and the Busselton Health Study [BHS], n = 4384), and we defined associations between APOE ε2 and ε4 and 569 plasma/serum lipid species. Mediation analysis defined the proportion of the treatment effect of the APOE genotype mediated by plasma/serum lipid species. RESULTS: A total of 237 and 104 lipid species were associated with APOE ε2 and ε4, respectively. Of these 68 (ε2) and 24 (ε4) were associated with prevalent Alzheimer's disease. Individual lipid species or lipidomic models of APOE genotypes mediated up to 30% and 10% of APOE ε2 and ε4 treatment effect, respectively. DISCUSSION: Plasma lipid species mediate the treatment effect of APOE genotypes on Alzheimer's disease and as such represent a potential therapeutic target. |
| format | Online Article Text |
| id | pubmed-9787288 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2022 |
| publisher | John Wiley and Sons Inc. |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-97872882022-12-27 APOE ε2 resilience for Alzheimer's disease is mediated by plasma lipid species: Analysis of three independent cohort studies Wang, Tingting Huynh, Kevin Giles, Corey Mellett, Natalie A Duong, Thy Nguyen, Anh Lim, Wei Ling Florence Smith, Alex AT Olshansky, Gavriel Cadby, Gemma Hung, Joseph Hui, Jennie Beilby, John Watts, Gerald F Chatterjee, Pratishtha Martins, Ian Laws, Simon M Bush, Ashley I Rowe, Christopher C Villemagne, Victor L Ames, David Masters, Colin L Taddei, Kevin Doré, Vincent Fripp, Jürgen Arnold, Matthias Kastenmüller, Gabi Nho, Kwangsik Saykin, Andrew J Baillie, Rebecca Han, Xianlin Martins, Ralph N Moses, Eric K Kaddurah‐Daouk, Rima Meikle, Peter J Alzheimers Dement Featured Articles INTRODUCTION: The apolipoprotein E (APOE) genotype is the strongest genetic risk factor for late‐onset Alzheimer's disease. However, its effect on lipid metabolic pathways, and their mediating effect on disease risk, is poorly understood. METHODS: We performed lipidomic analysis on three independent cohorts (the Australian Imaging, Biomarkers and Lifestyle [AIBL] flagship study, n = 1087; the Alzheimer's Disease Neuroimaging Initiative [ADNI] 1 study, n = 819; and the Busselton Health Study [BHS], n = 4384), and we defined associations between APOE ε2 and ε4 and 569 plasma/serum lipid species. Mediation analysis defined the proportion of the treatment effect of the APOE genotype mediated by plasma/serum lipid species. RESULTS: A total of 237 and 104 lipid species were associated with APOE ε2 and ε4, respectively. Of these 68 (ε2) and 24 (ε4) were associated with prevalent Alzheimer's disease. Individual lipid species or lipidomic models of APOE genotypes mediated up to 30% and 10% of APOE ε2 and ε4 treatment effect, respectively. DISCUSSION: Plasma lipid species mediate the treatment effect of APOE genotypes on Alzheimer's disease and as such represent a potential therapeutic target. John Wiley and Sons Inc. 2022-01-25 2022-11 /pmc/articles/PMC9787288/ /pubmed/35077012 http://dx.doi.org/10.1002/alz.12538 Text en © 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
| spellingShingle | Featured Articles Wang, Tingting Huynh, Kevin Giles, Corey Mellett, Natalie A Duong, Thy Nguyen, Anh Lim, Wei Ling Florence Smith, Alex AT Olshansky, Gavriel Cadby, Gemma Hung, Joseph Hui, Jennie Beilby, John Watts, Gerald F Chatterjee, Pratishtha Martins, Ian Laws, Simon M Bush, Ashley I Rowe, Christopher C Villemagne, Victor L Ames, David Masters, Colin L Taddei, Kevin Doré, Vincent Fripp, Jürgen Arnold, Matthias Kastenmüller, Gabi Nho, Kwangsik Saykin, Andrew J Baillie, Rebecca Han, Xianlin Martins, Ralph N Moses, Eric K Kaddurah‐Daouk, Rima Meikle, Peter J APOE ε2 resilience for Alzheimer's disease is mediated by plasma lipid species: Analysis of three independent cohort studies |
| title |
APOE ε2 resilience for Alzheimer's disease is mediated by plasma lipid species: Analysis of three independent cohort studies |
| title_full |
APOE ε2 resilience for Alzheimer's disease is mediated by plasma lipid species: Analysis of three independent cohort studies |
| title_fullStr |
APOE ε2 resilience for Alzheimer's disease is mediated by plasma lipid species: Analysis of three independent cohort studies |
| title_full_unstemmed |
APOE ε2 resilience for Alzheimer's disease is mediated by plasma lipid species: Analysis of three independent cohort studies |
| title_short |
APOE ε2 resilience for Alzheimer's disease is mediated by plasma lipid species: Analysis of three independent cohort studies |
| title_sort | apoe ε2 resilience for alzheimer's disease is mediated by plasma lipid species: analysis of three independent cohort studies |
| topic | Featured Articles |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9787288/ https://www.ncbi.nlm.nih.gov/pubmed/35077012 http://dx.doi.org/10.1002/alz.12538 |
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