A protein panel in cerebrospinal fluid for diagnostic and predictive assessment of Alzheimer’s disease
Open accessAbstract
Alzheimer’s disease (AD) is a neurodegenerative disease with heterogenous pathophysiological changes that develop years before the onset of clinical symptoms. These preclinical changes have generated considerable interest in identifying markers for the pathophysiological mechanisms linked to AD and AD-related disorders (ADRD). On the basis of our prior work integrating cerebrospinal fluid (CSF) and brain proteome networks, we developed a reliable and high-throughput mass spectrometry–selected reaction monitoring assay that targets 48 key proteins altered in CSF. To test the diagnostic utility of these proteins and compare them with existing AD biomarkers, CSF collected at baseline visits was assayed from 706 participants recruited from the Alzheimer’s Disease Neuroimaging Initiative. We found that the targeted CSF panel of 48 proteins (CSF 48 panel) performed at least as well as existing AD CSF biomarkers (Aβ 42 , tTau, and pTau 181 ) for predicting clinical diagnosis, FDG PET, hippocampal volume, and measures of cognitive and dementia severity. In addition, for each of those outcomes, the CSF 48 panel plus the existing AD CSF biomarkers significantly improved diagnostic performance. Furthermore, the CSF 48 panel plus existing AD CSF biomarkers significantly improved predictions for changes in FDG PET, hippocampal volume, and measures of cognitive decline and dementia severity compared with either measure alone. A potential reason for these improvements is that the CSF 48 panel reflects a range of altered biology observed in AD/ADRD. In conclusion, we show that the CSF 48 panel complements existing AD CSF biomarkers to improve diagnosis and predict future cognitive decline and dementia severity.
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There is important overlap between brain and CSF proteomes.
“Given the important overlap between brain and CSF proteomes, 80 , 81 , 82 further studies could investigate these proteins as potential sex‐specific biomarkers in AD.”
From Unraveling sex differences in Alzheimer's disease and related endophenotypes with brain proteomes (2025) · cites this paper as [82]
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Cerebrospinal fluid proteomics for predictive assessment of Alzheimer’s Disease riskPreprint
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Protein Panel in Cerebrospinal Fluid Helps Diagnose Alzheimer's and Track Progression
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- Authors
- Haque, R., Watson, C. M., Liu, J., Carter, E. K., Duong, D. M., Lah, J. J., Wingo, A. P., Roberts, B. R., Johnson, E. C. B., Saykin, A. J., Shaw, L. M., Seyfried, N. T., Wingo, T. S., & Levey, A. I.
- Affiliations
- Emory University (US)
- Indiana University Indianapolis (US)
- University of Pennsylvania (US)
- Corresponding author
- Seyfried, Nicholas T.
- Wingo, Thomas S.
- Levey, Allan I.
- ORCID
- Venue
- Science Translational Medicine
- Published
- 2023-09-06
- Volume
- 15
- Issue
- 712
- Pages
- eadg4122-eadg4122
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- PMC
- PMC10880442
- OpenAlex
- W4386469754
- Cited by
- 64
- References
- 33
- Citations by year
- 2026: 12 · 2025: 22 · 2024: 28 · 2023: 2
- FWCI
- 13.44
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science Translational Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- U.S. Department of Defense (W81XWH, W81XWH-12-2-, W81XWH1220012, AG024904)
- Alzheimer's Association (W81XWH-12-2-0012)
- Bristol-Myers Squibb (AG024904, W81XWH-12-2-0012)
- Eli Lilly and Company (AG024904, W81XWH-12-2-0012)
- Pfizer (AG024904, W81XWH-12-2-0012)
- Biogen (W81XWH-12-2-0012, AG024904)
- Meso Scale Diagnostics (AG024904, W81XWH-12-2-0012)
- Alzheimer's Disease Neuroimaging Initiative (W81XWH-12-2–0012, AG024904, W81XWH-12-2-)
- BioClinica (W81XWH-12-2-0012, AG024904)
- Novartis Pharmaceuticals Corporation (W81XWH-12-2-0012, AG024904)
- Siemens Medical Solutions USA
- Eisai (W81XWH-12-2-0012, AG024904)
- Servier (AG024904, W81XWH-12-2-0012)
- H. Lundbeck A/S (AG024904, W81XWH-12-2-0012)
- IXICO (AG024904, W81XWH-12-2-0012)
- National Institutes of Health (5u01ag024904-10, W81XWH, W81XWH-12-2-0012, AG024904, AG070937, AG066511)
- Genentech (W81XWH-12-2-0012, AG024904)
- Canadian Institutes of Health Research (W81XWH-12-2-0012)
- National Institute on Aging (U01-AG-024904, R01AG056533, U01AG061357, RF1AG062181, RF1AG057471, R01AG070937, U19AG024904, R01AG072120, R01AG061800, R01AG079170, R01AG075827, R01AG087250, U24AG021886, P30AG066511)
- National Heart, Lung, and Blood Institute
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- Alzheimer's disease, cerebrospinal fluid protein, cerebrospinal fluid biomarkers, preclinical Alzheimer's disease, diagnostic biomarkers, predictive biomarkers, cognitive decline, dementia severity, FDG-PET, hippocampal volume, tau protein, amyloid-beta, multiple reaction monitoring
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Cerebrospinal Fluid Proteins, Female, Hippocampus, Humans, Male, Middle Aged, Organ Size, Prognosis, Biomarkers, Endpoint Determination, Positron-Emission Tomography, High-Throughput Screening Assays
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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