Alzheimer’s Disease-Associated Cerebrospinal Fluid (CSF) Biomarkers do not Correlate with CSF Volumes or CSF Production Rate
Open accessAbstract
BACKGROUND: Neuropathologically, Alzheimer's disease (AD) is characterized by accumulation of a 42 amino acid peptide called amyloid-β (Aβ42) in extracellular senile plaques together with intraneuronal inclusions of hyperphosphorylated tau protein in neurofibrillary tangles and neuronal degeneration. These changes are reflected in the cerebrospinal fluid (CSF), the volumes and production rates of which vary considerably between individuals, by reduced concentration of Aβ42, increased concentration of phosphorylated tau (P-tau) protein, and increased concentration of total tau (T-tau) protein, respectively. OBJECTIVE: To examine the outstanding question if CSF concentrations of AD associated biomarkers are influenced by variations in CSF volumes, CSF production rate, and intracranial pressure in healthy individuals. METHODS: CSF concentrations of Aβ42, P-tau, and T-tau, as well as a number of other AD-related CSF biomarkers were analyzed together with intracranial subarachnoid, ventricular, and spinal CSF volumes, as assessed by magnetic resonance imaging volumetric measurements, and CSF production rate in 19 cognitively normal healthy subjects (mean age 70.6, SD 3.6 years). RESULTS: Negative correlations were seen between the concentrations of three CSF biomarkers (albumin ratio, Aβ38, and Aβ40), and ventricular CSF volume, but apart from this finding, no significant correlations were observed. CONCLUSION: These results speak against inter-individual variations in CSF volume and production rate as important confounds in the AD biomarker research field.
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Previous studies have demonstrated associations between individual CSF biomarkers (Aβ, T-tau, and P-tau) and ventricle volume, likely dilution effects.
“Previous studies have demonstrated associations between individual CSF biomarkers (for the AD biomarkers Aβ, T‐tau, and P‐tau) and ventricle volume (likely dilution effects; Edsbagge et al, 2017; van Waalwijk van Doorn et al, 2017), but to our knowledge, this is the first large‐scale study of such associations, and how they affect associations between CSF biomarker and genetic variants.”
From The genetic regulation of protein expression in cerebrospinal fluid (2023) · cites this paper as Edsbagge et al, 2017
The Abstract and Aβ-related markers section report negative associations between ventricular CSF volume and Aβ38 and Aβ40. But the Discussion says T-tau and P-tau were not associated with measured CSF volumes and explicitly rejects mere dilution as the explanation for the Aβ associations. (LLM, conf=0.88)
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Cites
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The genetic regulation of protein expression in cerebrospinal fluid
Hansson, O., Kumar, A., Janelidze, S., Stomrud, E., Insel, P. S., Blennow, K., Zetterberg, H., Fauman, E., Hedman, Å. K., Nagle, M. W., et al. (2023) · EMBO Molecular Medicine · doi:10.15252/emmm.202216359 · Cited by 56 · see citing works
Self-citation
- Authors
- Edsbagge, M., Andreasson, U., Ambarki, K., Wikkelsø, C., Eklund, A., Blennow, K., Zetterberg, H., & Tullberg, M.
- Affiliations
- University of Gothenburg (SE)
- Department of Psychiatry and Neurochemistry, Clinical Neurochemistry Laboratory,Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Umeå University (SE)
- UCL Queen Square Institute of Neurology (GB)
- Corresponding author
- Tullberg, Mats
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2017-06-05
- Volume
- 58
- Issue
- 3
- Pages
- 821-828
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W2613431089
- Cited by
- 17
- References
- 3
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 4 · 2019: 2
- FWCI
- 0.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, cerebrospinal fluid biomarkers
- MeSH terms
- Aged, Albumins, Alzheimer Disease, Cerebral Ventricles, Cerebrospinal Fluid, Female, Humans, Intracranial Pressure, Magnetic Resonance Imaging, Male, Organ Size, Peptide Fragments, Phosphorylation, Serum Albumin, Biomarkers, Amyloid beta-Peptides, tau Proteins
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