Quantitative proteomic profiling of cerebrospinal fluid to identify candidate biomarkers for Alzheimer’s disease
Open accessAbstract
Purpose: The aim of this study is to identify the potential cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease and to evaluate these markers on independent CSF samples using parallel reaction monitoring (PRM) assays. Experimental Design: High‐Resolution mass spectrometry and tandem mass tag (TMT) multiplexing technology are employed to identify potential biomarkers for Alzheimer's disease. Some of the identified potential biomarkers are validated using PRM assays. Results: A total of 2327 proteins are identified in the CSF of which 139 are observed to be significantly altered in the CSF of AD patients. The proteins altered in AD includes a number of known AD marker such as MAPT, NPTX2, VGF, GFAP, and NCAM1 as well as novel biomarkers such as PKM and YWHAG. These findings are validated in a separate set of CSF specimens from AD dementia patients and controls. NPTX2, in combination with PKM or YWHAG, leads to the best results with AUCs of 0.935 and 0.933, respectively. Conclusions and Clinical Relevance: The proteins that are found to be altered in the CSF of patients with AD could be used for monitoring disease progression and therapeutic response and perhaps also for early detection once they are validated in larger studies.
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The XO4+-specific HIF1A target protein PKM was recently identified as a novel AD CSF biomarker.
“the XO4+-specific HIF1A target protein PKM was recently identified as a novel AD CSF biomarker79.”
From Transcriptional signature in microglia associated with Aβ plaque phagocytosis (2021) · cites this paper as [79]
The Results and discussion (Targeted PRM analysis; page unavailable) identify PKM as a novel candidate AD CSF biomarker and report higher PKM levels in patients with AD. The paper does not describe PKM as XO4+-specific or as a HIF1A target, so those attributed descriptors are unsupported. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe 5 reference datasets were mined from 2 independent biofluid proteome studies of AD.
“The 5 reference datasets were mined from 2 independent biofluid proteome studies of AD [33, 34].”
From Integrated analysis of ultra-deep proteomes in cortex, cerebrospinal fluid and serum reveals a mitochondrial signature in Alzheimer’s disease (2020) · cites this paper as [34]
Several other groups used similar strategies in AD biomarker studies.
“In addition, several other groups used the similar strategies in AD biomarker studies [33, 34].”
From Integrated analysis of ultra-deep proteomes in cortex, cerebrospinal fluid and serum reveals a mitochondrial signature in Alzheimer’s disease (2020) · cites this paper as [34]
GPNMB emerged in this study and reference study 2 (data viii).
“GPNMB emerged in this study and reference study 2 (data viii) [34] (Fig. 3c, d).”
From Integrated analysis of ultra-deep proteomes in cortex, cerebrospinal fluid and serum reveals a mitochondrial signature in Alzheimer’s disease (2020) · cites this paper as [34]
The Results and discussion section on targeted PRM analysis names the candidate proteins examined, but does not mention GPNMB. Searches of our copy for “GPNMB” and “glycoprotein nonmetastatic melanoma protein B” found no passage establishing that it emerged in this study. Page numbers were not available in our copy. (LLM, conf=0.69)
Experimental — accuracy not yet measuredProteomics studies have identified neuronal pentraxins as deregulated in the CSF of patients with neurodegenerative diseases.
“Several proteomics studies have identified neuronal pentraxins to be deregulated in the CSF of patients with neurodegenerative diseases [22, 41, 42].”
LDHB, PKM, and DDAH1 have recently been reported as promising Alzheimer's disease cerebrospinal fluid biomarkers.
“LDHB, PKM, and DDAH1 have recently been reported as promising AD CSF biomarkers52,53.”
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- Authors
- Sathe, G., Na, C. H., Renuse, S., Madugundu, A. K., Albert, M., Moghekar, A., & Pandey, A.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Moghekar, Abhay
- Pandey, Akhilesh
- ORCID
- Venue
- PROTEOMICS – Clinical Applications
- Publisher
- Wiley
- Published
- 2019-01-25
- Volume
- 13
- Issue
- 4
- Pages
- e1800105-e1800105
- ISSN
- 1862-8346 (ISSN-L)
- 1862-8354
- PMC
- PMC6639119
- OpenAlex
- W2905951402
- Cited by
- 126
- References
- 57
- Citations by year
- 2026: 8 · 2025: 18 · 2024: 22 · 2023: 20 · 2022: 17 · 2021: 20 · 2020: 14 · 2019: 6 · 2017: 1
- FWCI
- 7.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- PROTEOMICS - CLINICAL APPLICATIONS (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion, other-oa)
- Funders
- National Institute on Aging (U19AG03365 (MA))
- National Institute of Neurological Disorders and Stroke (P50NS38377 (AP))
- National Science Foundation (S10OD021844)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, cerebrospinal fluid, biomarkers, quantitative proteomics, NPTX2, PKM, YWHAG, MAPT, VGF, glial fibrillary acidic protein, CD56, early detection, disease progression monitoring
- MeSH terms
- Pentraxins, Aged, Aged, 80 and over, Alzheimer Disease, C-Reactive Protein, Female, Humans, Male, Middle Aged, Nerve Tissue Proteins, Pyruvate Kinase, Biomarkers, Proteomics, 14-3-3 Proteins
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