期刊
SCIENCE ADVANCES
卷 6, 期 43, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.aaz9360
关键词
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资金
- National Institute on Aging [R01AG053960, R01AG057911, R01AG061800, RF1AG057471, RF1AG057470, R01AG057339, U01AG046161, U01AG061357]
- Emory ADRC [P50AG025688]
- NINDS Emory Neuroscience Core [P30NS055077]
- Foundation for the National Institutes of Health (FNIH)
- Alzheimer's Association (ALZ)
- Alzheimer's Research UK (ARUK)
- Michael J. Fox Foundation for Parkinson's Research (MJFF)
- Weston Brain Institute [11060]
Alzheimer's disease (AD) lacks protein biomarkers reflective of its diverse underlying pathophysiology, hindering diagnostic and therapeutic advancements. Here, we used integrative proteomics to identify cerebrospinal fluid (CSF) biomarkers representing a wide spectrum of AD pathophysiology. Multiplex mass spectrometry identified similar to 3500 and similar to 12,000 proteins in AD CSF and brain, respectively. Network analysis of the brain proteome resolved 44 biologically diverse modules, 15 of which overlapped with the CSF proteome. CSF AD markers in these overlapping modules were collapsed into five protein panels representing distinct pathophysiological processes. Synaptic and metabolic panels were decreased in AD brain but increased in CSF, while glial-enriched myelination and immunity panels were increased in brain and CSF. The consistency and disease specificity of panel changes were confirmed in >500 additional CSF samples. These panels also identified biological subpopulations within asymptomatic AD. Overall, these results are a promising step toward a network-based biomarker tool for AD clinical applications.
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