Please use this identifier to cite or link to this item:
https://ahro.austin.org.au/austinjspui/handle/1/28701| Title: | APOE ε2 resilience for Alzheimer's disease is mediated by plasma lipid species: Analysis of three independent cohort studies. | Austin Authors: | 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 | Affiliation: | Molecular Imaging and Therapy Medicine (University of Melbourne) The Florey Institute of Neuroscience and Mental Health Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia Lipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital, Perth, Western Australia Menzies Institute for Medical Research, University of Tasmania, Tasmania, Australia CSIRO Health and Biosecurity, Brisbane, Queensland, Australia Department of Biomedical Sciences, Macquarie University, North Ryde, New South Wales, Australia Centre for Precision Health, Edith Cowan University, Joondalup, Western Australia Department of Medicine, Duke University, Durham, North Carolina, USA Medical School, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Western Australia School of Population and Global Health, University of Western Australia, Perth, Western Australia, Australia Department of Molecular Imaging and Therapy, Austin Health, Melbourne, Victoria, Australia The Australian e-Health Research Centre, Health and Biosecurity, CSIRO, Melbourne, Victoria, Australia St George's Hospital, University of Melbourne Academic Unit for Psychiatry of Old Age, Kew, Victoria, Australia Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA Duke Institute of Brain Sciences, Duke University, Durham, North Carolina, USA PathWest Laboratory Medicine of Western Australia, Nedlands, Australia Monash University, Melbourne, Victoria, Australia KaRa Institute of Neurological Disease, Sydney, Macquarie Park, New South Wales, Australia Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, Victoria, Australia Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia Collaborative Genomics Group, School of Medical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia Department of Psychiatry and Behavioral Sciences, Duke University, Durham, North Carolina, USA Rosa & Co LLC, San Carlos, California, USA Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, USA Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana, USA Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, Indiana, USA Institute of Computational Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany National Ageing Research Institute, Parkville, Victoria, Australia |
Issue Date: | 25-Jan-2022 | Date: | 2022 | Publication information: | Alzheimer's & Dementia: the Journal of the Alzheimer's Association 2022; 18(11) | Abstract: | 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. 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. 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. Plasma lipid species mediate the treatment effect of APOE genotypes on Alzheimer's disease and as such represent a potential therapeutic target. | URI: | https://ahro.austin.org.au/austinjspui/handle/1/28701 | DOI: | 10.1002/alz.12538 | ORCID: | 0000-0001-8259-9069 0000-0003-3072-7940 0000-0003-3910-2453 0000-0002-5832-9875 0000-0002-8051-0558 |
Journal: | Alzheimer's & Dementia : The Journal of the Alzheimer's Association | PubMed URL: | 35077012 | PubMed URL: | https://pubmed.ncbi.nlm.nih.gov/35077012/ | Type: | Journal Article | Subjects: | APOE ε2 APOE ε4 Alzheimer's disease lipid species lipidomics mass spectrometry |
| Appears in Collections: | Journal articles |
Show full item record
Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.