Longitudinal stability of CSF biomarkers in Alzheimer's disease
Abstract
Biomarker levels in cerebrospinal fluid (CSF) may serve as surrogate markers for treatment efficacy in clinical trials of disease-modifying drugs against Alzheimer's disease (AD). A prerequisite, however, is that the marker is sufficiently stable over time in individual patients. Here, we tested the stability of the three established CSF biomarkers for AD, total tau (T-tau), tau phosphorylated at threonine 181 (P-tau(181)) and the 42 amino acid isoform of beta-amyloid (Abeta42), over 6 months in a cohort of AD patients on stable treatment with acetylcholinesterase (AChE) inhibitors. Fifty-three patients completed the study, 29 men and 24 women, mean age (+/-S.D.) 76.1+/-7.9 years. Mean levels of CSF biomarkers were very stable between baseline and endpoint, with coefficients of variation (CVs) of 4.4-6.1%. Intra-individual biomarker levels at baseline and endpoint were also highly correlated with Pearson r-values above 0.95 (p<0.0001), for all three markers. We conclude that T-tau, P-tau and Abeta42 concentrations in CSF are remarkably stable over a 6-month period in individual AD patients. This suggest that these biomarkers may have a potential to identify and monitor very minor biochemical changes induced by treatment, and thus support their possible usefulness as surrogate markers in clinical trials with drug candidates with disease-modifying potential, such as secretase inhibitors, Abeta immunotherapy and tau phosphorylation inhibitors.
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Longitudinal stability of protein biomarkers has been considered a critical factor for the reliability of biomarkers.
“While the longitudinal stability of protein biomarkers has been considered as a critical factor for the reliability of biomarkers25”
From Intra- and Inter-individual Variability of microRNA Levels in Human Cerebrospinal Fluid: Critical Implications for Biomarker Discovery (2017) · cites this paper as [25]
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- Authors
- Blennow, K., Zetterberg, H., Minthon, L., Lannfelt, L., Strid, S., Annas, P., Basun, H., & Andreasen, N.
- Affiliations
- Sahlgrenska University Hospital (SE)
- Lund University (SE)
- Uppsala University (SE)
- AstraZeneca (Sweden) (SE)
- Karolinska University Hospital (SE)
- Corresponding author
- Blennow, Kaj
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 2007-05
- Volume
- 419
- Issue
- 1
- Pages
- 18-22
- ISSN
- 0304-3940 (ISSN-L)
- OpenAlex
- W2000566928
- Cited by
- 193
- References
- 3
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 8 · 2020: 7 · 2019: 4 · 2018: 10 · 2017: 4 · 2016: 8 · 2015: 6 · 2014: 18 · 2013: 17 · 2012: 12
- FWCI
- 14.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience Letters (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Keywords
- Alzheimer's disease, cerebrospinal fluid biomarkers, longitudinal stability, total tau, amyloid-beta 42, acetylcholinesterase inhibitors, surrogate markers, treatment monitoring, disease-modifying drugs, secretase inhibitors
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Analysis of Variance, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Peptide Fragments, Biomarkers, Amyloid beta-Peptides, tau Proteins
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