Amyloid-β and Tau Dynamics in Human Brain Interstitial Fluid in Patients with Suspected Normal Pressure Hydrocephalus
Abstract
BACKGROUND: Amyloid-β (Aβ1 - 42), total tau (T-tau), and phosphorylated tau (P-tau181) in the cerebrospinal fluid (CSF) are the most promising biomarkers of Alzheimer's disease (AD). Still, little is known about the dynamics of these molecules in the living brain. In a transgenic mouse brain, soluble Aβ decreases with increasing age and advanced Aβ pathology as seen similarly in CSF. OBJECTIVE: To assess the relationship between AD-related pathological changes in human brain tissue, ventricular and lumbar CSF, and brain interstitial fluid (ISF). METHODS: Altogether 11 patients with suspected idiopathic normal pressure hydrocephalus underwent frontal cortical brain biopsy, 24-h intraventricular pressure monitoring, and a microdialysis procedure. AD-related biomarkers were analyzed from brain tissue, CSF, and ISF. RESULTS: ISF T-tau levels decreased strongly within the first 12 h, then plateauing until the end of the experiment. Aβ1 - 42 and P-tau181 remained stable during the experiment (n = 3). T-tau and P-tau were higher in the ISF than in ventricular or lumbar CSF, while Aβ1 - 42 levels were within similar range in both CSF and ISF samples. ISF P-tau correlated with the ventricular CSF T-tau (r = 0.70, p = 0.017) and P-tau181 (r = 0.64, p = 0.034). Five patients with amyloid pathology in the brain biopsy tended to reveal lower ISF Aβ1 - 42 levels than those six without amyloid pathology. CONCLUSIONS: This is the first study to report ISF Aβ and tau levels in the human brain without significant brain injury. The set-up used enables sampling from the brain ISF for at least 24 h without causing adverse effects due to the microdialysis procedure to follow the dynamics of the key molecules in AD pathogenesis in the living brain at various stages of the disease.
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Tau is present in the interstitial space both in tauopathy animal models and in the human brain.
“Furthermore, tau is now known to be present in the interstitial space both in tauopathy animal models234 and in the human brain236.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [236]
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- Authors
- Herukka, S.-K., Rummukainen, J., Ihalainen, J., von und zu Fraunberg, M., Koivisto, A. M., Nerg, O., Puli, L. K., Seppälä, T. T., Zetterberg, H., Pyykkö, O. T., Helisalmi, S., Tanila, H., Alafuzoff, I., Hiltunen, M., Rinne, J., Soininen, H., Jääskeläinen, J. E., & Leinonen, V.
- Affiliations
- University of Eastern Finland (FI)
- Kuopio University Hospital (FI)
- Neurosurgery of NeuroCenter, Kuopio University Hospital, Kuopio, Finland and Neurosurgery, Institute of Clinical Medicine, University of Eastern Finland Kuopio, Finland
- National Hospital for Neurology and Neurosurgery (GB)
- Uppsala University (SE)
- University of Turku (FI)
- Corresponding author
- Leinonen, Ville
- ORCID
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2015-05-07
- Volume
- 46
- Issue
- 1
- Pages
- 261-269
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W1613370405
- Cited by
- 43
- References
- 27
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 2 · 2023: 2 · 2022: 6 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 10 · 2017: 6 · 2016: 3 · 2015: 1
- FWCI
- 4.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Academy of Finland
- Israel Science Foundation
- Kuopion Yliopistollinen Sairaala
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- amyloid-beta, tau protein
- MeSH terms
- Aged, Aged, 80 and over, Brain, Cognition Disorders, Female, Humans, Hydrocephalus, Normal Pressure, Male, Middle Aged, Peptide Fragments, Chi-Square Distribution, Amyloid beta-Peptides, tau Proteins, Microdialysis, Extracellular Fluid, Apolipoprotein E4
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