期刊
ALZHEIMERS & DEMENTIA
卷 -, 期 -, 页码 -出版社
WILEY
DOI: 10.1002/alz.12800
关键词
APOE; APP; autosomal dominant Alzheimer's disease; beta-citrylglutamate; lipidomics; metabolomics; PSEN1; PSEN2; TREM2
资金
- Dominantly Inherited Alzheimer Network (DIAN) - National Institute on Aging (NIA) [U19AG032438]
- Alzheimer's Association [SG-20-690363-DIAN]
- German Center for Neurodegenerative Diseases (DZNE)
- Raul Carrea Institute for Neurological Research (FLENI)
- Research and Development Grants for Dementia from Japan Agency for Medical Research and Development
- AMED
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI)
- Spanish Institute of Health Carlos III (ISCIII)
- Canadian Institutes of Health Research (CIHR)
- Canadian Consortium of Neurodegeneration and Aging
- Brain Canada Foundation
- Fonds de Recherche du Quebec - Sante
- NIA [R01AG046171, RF1AG051550, 3U01AG024904-09S4, RF1AG057452, R01AG059093, RF1AG058942, U01AG061359, U19AG063744]
- FNIH [DAOU16AMPA]
- Alzheimer's Disease Neuroimaging Initiative (ADNI) [U01 AG024904]
- DOD ADNI [W81XWH-12-2-0012]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- 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
- 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
- Transition Therapeutics
- Canadian Institutes of Health Research
- The NIA [P30AG10161, R01AG1581, R01AG17917, R01AG30146, R01AG36042, RC2AG036547, R01AG36836, R01AG48015, RF1AG57473, U01AG32984, U01AG46152, U01AG46161, U01AG61356, 3R01AG046171-02S2, R01AG15819, U01AG32984 U01AG46152]
- Illinois Department of Public Health
- Translational Genomics Research Institute
- National Institute of Health [NIA R01AG057777, RO1AG057777-02S1, K99AG061281, P30AG066444, P01AGO26276, NINDS R01NS118146, R01AG044546, P01AG003991, RF1AG053303, RF1AG058501, U01AG058922]
- Chan Zuckerberg Initiative (CZI)
Metabolomic analysis reveals distinct metabolic features in carriers of different genetic risk factors for Alzheimer's disease, providing insights into the etiology and clinical presentation of the disease.
Introduction: The identification of multiple genetic risk factors for Alzheimer's disease (AD) suggests that many pathways contribute to AD onset and progression. However, the metabolomic and lipidomic profiles in carriers of distinct genetic risk factors are not fully understood. The metabolome can provide a direct image of dysregulated pathways in the brain. Methods: We interrogated metabolomic signatures in the AD brain, including carriers of pathogenic variants in APP, PSEN1, and PSEN2 (autosomal dominant AD; ADAD), APOE epsilon 4, and TREM2 risk variant carriers, and sporadic AD (sAD). Results: We identified 133 unique and shared metabolites associated with ADAD, TREM2, and sAD. We identified a signature of 16 metabolites significantly altered between groups and associated with AD duration. Discussion: AD genetic variants show distinct metabolic perturbations. Investigation of these metabolites may provide greater insight into the etiology of AD and its impact on clinical presentation.
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