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Open Access 01-12-2014 | Methodology

Identification of longitudinally dynamic biomarkers in Alzheimer’s disease cerebrospinal fluid by targeted proteomics

Authors: Kristin R Wildsmith, Stephen P Schauer, Ashley M Smith, David Arnott, Yuda Zhu, Joshua Haznedar, Surinder Kaur, W Rodney Mathews, Lee A Honigberg

Published in: Molecular Neurodegeneration | Issue 1/2014

Abstract

Background

Alzheimer’s disease (AD) is the leading cause of dementia affecting greater than 26 million people worldwide. Although cerebrospinal fluid (CSF) levels of Aβ₄₂, tau, and p-tau₁₈₁ are well established as diagnostic biomarkers of AD, there is a need for additional CSF biomarkers of neuronal function that continue to change during disease progression and could be used as pharmacodynamic measures in clinical trials. Multiple proteomic discovery experiments have reported a range of CSF biomarkers that differ between AD and control subjects. These potential biomarkers represent multiple aspects of the disease pathology. The performance of these markers has not been compared with each other, and their performance has not been evaluated longitudinally.

Results

We developed a targeted-proteomic, multiple reaction monitoring (MRM) assay for the absolute quantitation of 39 peptides corresponding to 30 proteins. We evaluated the candidate biomarkers in longitudinal CSF samples collected from aged, cognitively-normal control (n = 10), MCI (n = 5), and AD (n = 45) individuals (age > 60 years). We evaluated each biomarker for diagnostic sensitivity, longitudinal consistency, and compared with CSF Aβ₄₂, tau, and p-tau₁₈₁. Four of 28 quantifiable CSF proteins were significantly different between aged, cognitively-normal controls and AD subjects including chitinase-3-like protein 1, reproducing published results. Four CSF markers demonstrated significant longitudinal change in AD: Amyloid precursor protein, Neuronal pentraxin receptor, NrCAM and Chromogranin A. Robust correlations were observed within some subgroups of proteins including the potential disease progression markers.

Conclusion

Using a targeted proteomics approach, we confirmed previous findings for a subset of markers, defined longitudinal performance of our panel of markers, and established a flexible proteomics method for robust multiplexed analyses.

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Title: Identification of longitudinally dynamic biomarkers in Alzheimer’s disease cerebrospinal fluid by targeted proteomics
Authors: Kristin R Wildsmith
Stephen P Schauer
Ashley M Smith
David Arnott
Yuda Zhu
Joshua Haznedar
Surinder Kaur
W Rodney Mathews
Lee A Honigberg
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Molecular Neurodegeneration / Issue 1/2014
Electronic ISSN: 1750-1326
DOI: https://doi.org/10.1186/1750-1326-9-22

ACC 2024 Congress

Springer Medicine

Identification of longitudinally dynamic biomarkers in Alzheimer’s disease cerebrospinal fluid by targeted proteomics

Abstract

Background

Results

Conclusion

ACC 2024 Congress

Springer Medicine

Abstract

Background

Results

Conclusion

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