Journal article

Concordant peripheral lipidome signatures in two large clinical studies of Alzheimer's disease

Kevin Huynh, Wei Ling Florence Lim, Corey Giles, Kaushala S Jayawardana, Agus Salim, Natalie A Mellett, Adam Alexander T Smith, Gavriel Olshansky, Brian G Drew, Pratishtha Chatterjee, Ian Martins, Simon M Laws, Ashley I Bush, Christopher C Rowe, Victor L Villemagne, David Ames, Colin L Masters, Matthias Arnold, Kwangsik Nho, Andrew J Saykin Show all

Nature Communications | NATURE RESEARCH | Published : 2020

Abstract

Changes to lipid metabolism are tightly associated with the onset and pathology of Alzheimer's disease (AD). Lipids are complex molecules comprising many isomeric and isobaric species, necessitating detailed analysis to enable interpretation of biological significance. Our expanded targeted lipidomics platform (569 species across 32 classes) allows for detailed lipid separation and characterisation. In this study we examined peripheral samples of two cohorts (AIBL, n = 1112 and ADNI, n = 800). We are able to identify concordant peripheral signatures associated with prevalent AD arising from lipid pathways including; ether lipids, sphingolipids (notably GM3 gangliosides) and lipid classes pre..

View full abstract

Grants

Awarded by CRC Program


Awarded by NIA's national initiatives AMP-AD


Awarded by NCI


Awarded by Qatar National Research Fund


Awarded by National Institutes of Health


Funding Acknowledgements

Funding for the AIBL study was provided in part by the study partners [Commonwealth Scientific Industrial and research Organization (CSIRO), Edith Cowan University (ECU), Mental Health Research institute (MHRI), National Ageing Research Institute (NARI), Austin Health, CogState Ltd]. The AIBL study has also received support from the National Health and Medical Research Council (NHMRC) and the Dementia Collaborative Research Centres program (DCRC2), as well as funding from the Science and Industry Endowment Fund (SIEF) and the Cooperative Research Centre (CRC) for Mental Health-funded through the CRC Program (Grant ID:20100104), an Australian Government Initiative. This work was also supported in part by the Victorian Government's Operational Infrastructure Support Program. K.H. was supported by a Dementia Australia Research Foundation Scholarship. P.J.M. is supported by a Senior Research Fellowship from the National Health and Medical Research Council of Australia. Support for the metabolomics sample processing, assays and analytics reported here was provided by grants from the National Institute on Aging (NIA); NIA supported the Alzheimer's Disease Metabolomics Consortium which is a part of NIA's national initiatives AMP-AD and M<SUP>2</SUP>OVE-AD (R01 AG046171, RF1 AG051550, RF1 AG057452 and 3U01 AG024904-09S4). Additional NIH support from the NIA, NLM and NCI for analysis includes P30 AG10133, R01 AG19771, R01 LM012535, R03 AG054936, R01 AG061788, K01 AG049050 and R01 CA129769. M.A. is supported by National Institute on Aging grants RF1 AG057452, RF1 AG058942, RF1 AG059093 and U01 AG061359. M.A. is also supported by funding from Qatar National Research Fund NPRP8-061-3-011. K.N. is supported by NLM R01 LM012535 and NIA R03AG054936. Data collection and sharing for the ADNI was supported by National Institutes of Health Grant U01 AG024904. ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd; Janssen Alzheimer Immunotherapy Research & Development, LLC; Johnson & Johnson Pharmaceutical Research & Development LLC; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. This study was only possible with the help of the AIBL research group. The authors who made direct contribution to this study have been listed as authors in this article. Members of the AIBL group who did not participate in the analysis or writing of this report are listed here: https://aibl.csiro.au/about/aibl-research-team/. Part of the data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). The authors who made direct contribution to this study have been listed as authors in this article. As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf. Part of the data used in preparation of this article were generated by the Alzheimer's Disease Metabolomics Consortium (ADMC). The authors who made direct contribution to this study have been listed as authors in this article. Investigators within the ADMC provided data but did not participate in analysis or writing of this report can be found at https://sites.duke.edu/adnimetab/team/.