Mass-Spectrometry-Based Method To Quantify in Parallel Tau and Amyloid β 1–42 in CSF for the Diagnosis of Alzheimer’s Disease
Open accessAbstract
Alzheimer’s disease (AD), the most common form of dementia, afflicts about 50 million people worldwide. Currently, AD diagnosis is primarily based on psychological evaluation and can only be confirmed post-mortem. Reliable and objective biomarkers for prognosis and diagnosis have been sought for years. Together, tau and amyloid β 1–42 (Aβ 42 ) in cerebrospinal fluid (CSF) have been shown to provide good diagnostic sensitivity and specificity. Additionally, phosphorylated forms of tau, such as tau pS181, have also shown promising results. However, the measurement of such markers currently relies on antibody-based immunoassays that have shown variability, leading to discrepant results across laboratories. To date, mass spectrometry methods developed to evaluate CSF tau and Aβ 42 are not compatible. We present in this article the development of a mass-spectrometry-based method of quantification for CSF tau and Aβ 42 in parallel. The absolute concentrations of tau and Aβ 42 we measured are on average 50 ng/mL (7–130 ng/mL) and 7.1 ng/mL (3–13 ng/mL), respectively. Analyses of CSF tau and Aβ 42, in a cohort of patients with AD, mild cognitive impairment, and healthy controls (30 subjects), provide significant group differences evaluated with ROC curves (AUC (control-AD) and AUC (control-MCI) = 1, AUC (MCI-AD) = 0.76), with at least equivalent diagnostic utility to immunoassay measurements in the same sample set. Finally, a significant and negative correlation was found between the tau and Aβ peptides ratio and the disease severity.
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Several studies have successfully used targeted MS strategies to quantify Aβ, tau, and APOE protein levels in CSF with similar disease-association efficacy to that of traditional ELISA assays.
“Several studies have successfully used targeted MS strategies to quantify Aβ, tau, and APOE protein levels in CSF with similar disease-association efficacy to that of traditional ELISA assays [189–191].”
From Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau (2021) · cites this paper as [190]
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- Authors
- Pottiez, G., Yang, L., Stewart, T., Song, N., Aro, P., Galasko, D. R., Quinn, J. F., Peskind, E. R., Shi, M., & Zhang, J.
- Affiliations
- University of Washington (US)
- University of California San Diego (US)
- Oregon Health & Science University (US)
- Corresponding author
- Zhang, Jing
- ORCID
- Venue
- Journal of Proteome Research
- Publisher
- American Chemical Society (ACS)
- Published
- 2017-02-07
- Volume
- 16
- Issue
- 3
- Pages
- 1228-1238
- ISSN
- 1535-3893 (ISSN-L)
- 1535-3907
- PMC
- PMC5679294
- OpenAlex
- W2580679988
- Cited by
- 37
- References
- 38
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 6 · 2022: 2 · 2021: 5 · 2020: 6 · 2019: 2 · 2018: 5 · 2017: 2 · 2016: 1
- FWCI
- 3.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Proteome Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Environmental Health Sciences (P30 ES007033-8649, R01 ES016873, R01 ES019277)
- National Institute of Neurological Disorders and Stroke (U01 NS082137, U01 NS091272)
- National Institute on Aging (P50 AG05131)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, cerebrospinal fluid, tau protein, amyloid-beta 42, mass spectrometry quantification, biomarkers, mild cognitive impairment, disease severity, immunoassay comparison, sensitivity and specificity
- MeSH terms
- Alzheimer Disease, Humans, Peptide Fragments, ROC Curve, Sensitivity and Specificity, Severity of Illness Index, Mass Spectrometry, Biomarkers, Case-Control Studies, Amyloid beta-Peptides, tau Proteins
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