Related Experiment Video
Updated: May 29, 2026
08:17
In Vivo Microdialysis Method to Collect Large Extracellular Proteins from Brain Interstitial Fluid with High-molecular Weight Cut-off Probes
Published on: September 26, 2018
In vivo microdialysis reveals age-dependent decrease of brain interstitial fluid tau levels in P301S human tau
Kaoru Yamada1, John R Cirrito, Floy R Stewart
1Department of Neurology, Hope Center for Neurological Disorders, Washington University, St. Louis, Missouri 63110, USA.
Summary
Extracellular tau protein is present in brain interstitial fluid (ISF) and is higher than in CSF. Monomeric ISF tau levels decrease with tau aggregation, suggesting a link between tau release and pathology spread.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Tau protein, typically cytoplasmic, is found in extracellular fluids like CSF.
- Extracellular tau aggregates may facilitate the spread of tau pathology between cells.
- The release and dynamics of tau in brain interstitial fluid (ISF) remain poorly understood.
Purpose of the Study:
- To investigate the normal release of tau into brain ISF.
- To compare ISF tau concentration with cerebrospinal fluid (CSF) tau levels.
- To determine if tau aggregation influences ISF tau levels.
Main Methods:
- Developed a microdialysis technique for analyzing monomeric ISF tau in awake mice.
- Measured ISF tau in wild-type and P301S human tau transgenic mice.
- Analyzed brain homogenates and assessed the impact of injected tau fibrils on ISF tau.
Main Results:
- Detected tau in the ISF of wild-type mice, indicating normal release.
- ISF tau levels were significantly higher than CSF tau levels and not correlated.
- Monomeric ISF tau decreased significantly after the onset of tau aggregation in P301S mice.
Conclusions:
- Tau is released into the brain ISF under normal physiological conditions.
- ISF tau levels are higher than CSF tau and are inversely related to tau aggregation.
- Extracellular tau may be in equilibrium with intracellular or extracellular tau aggregates, impacting tau pathology spread.
