期刊
出版社
WILEY
DOI: 10.1002/dad2.12286
关键词
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资金
- ZonMW Memorabel grant programme [733050824]
- Innovative Medicines Initiative Joint Undertaking under EMIF-AD MBD grant [115372]
- Swedish Research Council [2018-02532]
- European Research Council [681712]
- Swedish State Support for Clinical Research [ALFGBG-720931]
- Alzheimer Drug Discovery Foundation (ADDF), USA [201809-2016862]
- AD Strategic Fund [ADSF-21-831376-C, ADSF-21-831381-C, ADSF-21-831377-C]
- Alzheimer's Association [ADSF-21-831376-C, ADSF-21-831381-C, ADSF-21-831377-C]
- Olav Thon Foundation
- Erling-Persson Family Foundation
- Stiftelsen for Gamla Tjanarinnor, Hjarnfonden, Sweden [FO2019-0228]
- European Union's Horizon 2020 research and innovation programme under the Marie Skodowska-Curie grant [860197]
- UK Dementia Research Institute at UCL
- Alzheimerfonden [AF-930934]
- Alzheimer's Disease Neuroimaging Initiative (ADNI
- National Institutes of Health) [U01 AG024904]
- DOD ADNI (Department of Defense award) [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
- 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
- Stiftelsen for Gamla Tjanarinnor
This study investigated changes in cerebrospinal fluid proteomics with age and found that certain proteins increased with age regardless of amyloid status, associated with immune and signaling processes. On the other hand, some proteins decreased with age specifically in amyloid abnormal participants and were linked to extracellular matrix organization, suggesting physiological aging and early AD pathology.
Introduction It is important to understand which biological processes change with aging, and how such changes are associated with increased Alzheimer's disease (AD) risk. We studied how cerebrospinal fluid (CSF) proteomics changed with age and tested if associations depended on amyloid status, sex, and apolipoprotein E sigma 4 genotype. Methods We included 277 cognitively intact individuals aged 46 to 89 years from Alzheimer's Disease Neuroimaging Initiative, European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery, and Metabolic Syndrome in Men. In total, 1149 proteins were measured with liquid chromatography mass spectrometry with multiple reaction monitoring/Rules-Based Medicine, tandem mass tag mass spectrometry, and SOMAscan. We tested associations between age and protein levels in linear models and tested enrichment for Reactome pathways. Results Levels of 252 proteins increased with age independently of amyloid status. These proteins were associated with immune and signaling processes. Levels of 21 proteins decreased with older age exclusively in amyloid abnormal participants and these were enriched for extracellular matrix organization. Discussion We found amyloid-independent and -dependent CSF proteome changes with older age, perhaps representing physiological aging and early AD pathology.
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