Age-Dependent Changes in the Cerebrospinal Fluid Proteome by Slow Off-Rate Modified Aptamer Array
Open accessAbstract
An important precondition for the successful development of diagnostic assays of cerebrospinal fluid (CSF) biomarkers of age-related neurodegenerative diseases is an understanding of the dynamic nature of the CSF proteome during the normal aging process. In this study, a novel proteomic technology was used to quantify hundreds of proteins simultaneously in the CSF from 90 cognitively normal adults 21 to 85 years of age. SomaLogic's highly multiplexed proteomic platform can measure more than 800 proteins simultaneously from small volumes of biological fluids using novel slow off-rate modified aptamer (SOMAmer) protein affinity reagents with sensitivity, specificity, and dynamic ranges that meet or exceed those of enzyme-linked immunosorbent assays. In the first application of this technology to CSF, we detected 248 proteins that possessed signals greater than twofold over background. Several novel correlations between detected protein concentrations and age were discovered that indicate that both inflammation and response to injury in the central nervous system may increase with age. Applying this powerful proteomic approach to CSF provides potential new insight into the aging of the human central nervous system that may have utility in discovering new disease-related changes in the CSF proteome.
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Baird et al. and Menni et al. developed the first ageing clock models based on the SomaLogic aptamer-based proteomic platform using human cerebrospinal fluid and plasma samples, respectively, although associations with any ageing phenotypes or organ function were not examined.
“Pioneering studies by Baird et al.94 and Menni et al.91 developed the first ageing clock models based on the SomaLogic aptamer-based proteomic platform using human cerebrospinal fluid and plasma samples, respectively, although associations with any ageing phenotypes or organ function were not examined.”
From Measuring biological age using omics data (2022) · cites this paper as [94]
Studies using multiple proteomic technologies have shown that thousands of proteins change with age in human plasma and cerebrospinal fluid.
“Studies using multiple proteomic technologies have shown that thousands of proteins change with age in human plasma91–93 and cerebrospinal fluid94, which has recently led to the development of multiple proteomic ageing clocks.”
From Measuring biological age using omics data (2022) · cites this paper as [94]
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- Authors
- Baird, G. S., Nelson, S. K., Keeney, T. R., Stewart, A., Williams, S., Kraemer, S., Peskind, E. R., & Montine, T. J.
- Affiliations
- University of Washington (US)
- SomaLogic (United States) (US)
- Corresponding author
- Baird, Geoffrey S.
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2012-02
- Volume
- 180
- Issue
- 2
- Pages
- 446-456
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC3349859
- OpenAlex
- W2017978637
- Cited by
- 110
- References
- 57
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 13 · 2023: 6 · 2022: 11 · 2021: 8 · 2020: 12 · 2019: 4 · 2018: 10 · 2017: 5 · 2016: 4 · 2015: 7 · 2014: 9 · 2013: 4 · 2012: 3
- FWCI
- 2.32
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- American Journal Of Pathology (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (AG05136)
- U.S. Department of Veterans Affairs
- Nancy and Buster Alvord Endowment
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced Biosensing Techniques and Applications
- Keywords
- cerebrospinal fluid proteome, aging, age-related neurodegenerative diseases, biomarkers, SOMAmer, multiplexed protein quantification, neuroinflammation, injury response, cognitive aging
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Cerebrospinal Fluid Proteins, Female, Humans, Male, Middle Aged, Biomarkers, Proteome, Protein Array Analysis, Aptamers, Nucleotide, Young Adult
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