Cited by 66Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsAdvanced Proteomics Techniques and Applications

A protein panel in cerebrospinal fluid for diagnostic and predictive assessment of Alzheimer’s disease

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Haque, Rafi, Watson, Caroline M., Liu, Jiaqi, Carter, E. Kathleen, Duong, Duc M., Lah, James J., Wingo, Aliza P., Roberts, Blaine R. +6 more·2023·Science Translational Medicine

Abstract

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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  1. [26]Zhou M, Haque RU, Dammer EB, Duong DM, Ping L, Johnson ECB, Lah JJ, Levey AI, Seyfried NT, Targeted mass spectrometry to quantify brain-derived cerebrospinal fluid biomarkers in Alzheimer’s disease. Clin Proteomics 17, 19 (2020). 32514259 PMC7257173

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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.
Venue
Science Translational Medicine
Published
2023-09-06
Volume
15
Issue
712
Pages
eadg4122-eadg4122
ISSN
  • 1946-6234 (ISSN-L)
  • 1946-6242
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
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

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