2011
DOI: 10.1523/jneurosci.2569-11.2011
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In VivoMicrodialysis Reveals Age-Dependent Decrease of Brain Interstitial Fluid Tau Levels in P301S Human Tau Transgenic Mice

Abstract: Although tau is a cytoplasmic protein, it is also found in brain extracellular fluids, e.g., CSF. Recent findings suggest that aggregated tau can be transferred between cells and extracellular tau aggregates might mediate spread of tau pathology. Despite these data, details of whether tau is normally released into the brain interstitial fluid (ISF), its concentration in ISF in relation to CSF, and whether ISF tau is influenced by its aggregation are unknown. To address these issues, we developed a microdialysi… Show more

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Cited by 318 publications
(350 citation statements)
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“…The origin of CSF-Tau is not clear, but dying and disintegrating neurons could contribute to it. In fact, recent microdialysis experiments suggest that Tau is even higher in the interstitial fluid (Yamada et al 2011). Another recent development is derived from the earlier observation that Tau pathology spreads in the brain in a well-defined manner, so that its distribution can be correlated with the clinical stages of the disease (Braak stages;Braak and Braak 1991).…”
Section: Tau Protein In Neurofibrillary Degenerationmentioning
confidence: 99%
“…The origin of CSF-Tau is not clear, but dying and disintegrating neurons could contribute to it. In fact, recent microdialysis experiments suggest that Tau is even higher in the interstitial fluid (Yamada et al 2011). Another recent development is derived from the earlier observation that Tau pathology spreads in the brain in a well-defined manner, so that its distribution can be correlated with the clinical stages of the disease (Braak stages;Braak and Braak 1991).…”
Section: Tau Protein In Neurofibrillary Degenerationmentioning
confidence: 99%
“…In vivo microdialysis experiments to assess brain ISF tau levels from awake and freely moving mice were developed with modifications of our previously described method (Yamada et al, 2011). A guide cannula (Eicom microdialysis) was stereotactically implanted in the left hippocampus under isoflurane anesthesia, and cemented.…”
Section: In Vivo Microdialysismentioning
confidence: 99%
“…The tau concentration in media of brain slice culture and ISF of wild-type mice was analyzed in a tau sandwich ELISA with Tau-5 as a coating antibody (gift from L. Binder, Northwestern University, Evanston, IL) and biotinylated BT-2 (Thermo Fisher Scientific) as a detection antibody as previously described (Yamada et al, 2011). Human tau in ISF and brains was measured by a human tau-specific sandwich ELISA with Tau-5 as a coating antibody and biotinylated human specific HT-7 (Thermo Fisher Scientific) as a detection antibody.…”
Section: Animalsmentioning
confidence: 99%
“…These results are consistent with a local shift of soluble tau to a more aggregated, insoluble form that would not be detected by microdialysis. In contrast, increased CSF tau seems to reflect the neurodegeneration observed in these mice, consistent with an increased cellular release of tau in disease [52]. However, tau levels do not correlate with lactate dehydrogenase or tubulin release into the media [53,54], implying that release is not due to increased cell death.…”
Section: Escape Of Aggregates From Neuronsmentioning
confidence: 66%
“…2a). Monomeric tau is clearly released from cells, as tau has been found in the interstitial fluid (ISF) of wild-type mice in the absence of injury or neurodegeneration [52]. Mice expressing aggregation-prone mutant P301S tau have demonstrated a drop in soluble ISF tau and an increase in CSF levels, associated with intracellular aggregation (the microdialysis probe used in this study cannot measure tau aggregates).…”
Section: Escape Of Aggregates From Neuronsmentioning
confidence: 90%