# Tau Kinetics in the human CNS in vivo and in vitro

> **NIH NIH K01** · WASHINGTON UNIVERSITY · 2020 · $119,326

## Abstract

Project Abstract/Summary
 The overall goal of this research is to understand the pathophysiology of tau protein in the human central
nervous system (CNS). Specifically, I will test the hypothesis that tau protein kinetics are altered in
tauopathies such as Alzheimer’s disease (AD).
 Tau aggregation in the brain and alterations in cerebrospinal fluid (CSF) tau are hallmarks of AD and
other tauopathies such as Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD).
Previous studies suggest that CSF tau continuously increases with age and cognitive decline, and CSF
total tau, CSF phosphorylated tau, and CSF amyloid beta (Ab) are currently used as AD biomarkers.
However, recent study indicates that this is not linear, and CSF tau decreases after symptom onset.
Therefore, it is critical to understand and evaluate tau metabolism more comprehensively in order to use it
as a true biomarker that would precisely predict age of onset and progress of the disease. Currently the
mechanism of CSF tau alterations, especially in humans, remains unclear. Is the increased CSF tau due to
increased tau production or decreased clearance? Does pathological condition such as increasing Ab
burden alter tau kinetics?
 To measure the tau kinetics in the human central nervous system (CNS), I developed stable isotope
labeling kinetics (SILK) method for tau. In Aim 1, 30 AD patients, 40 cognitively normal age-matched
participants, 30 younger controls, and up to 35 non-AD tauopathies including PSP, CBD, and MAPT
mutation families will be analyzed with the tau SILK methods to test the hypothesis that tau kinetics are
altered in tauopathies. In Aim 2, I will use in vitro tau SILK method in neuronal cell cultures including
induced pluripotent stem cell (iPSCs)-derived neurons to test the hypothesis that tau production is
increased in AD, with increasing amyloid. This proposal will help design future clinical studies and
ultimately develop novel therapeutic strategies targeting tau.
 Successful funding of this mentored career development award will afford me an extraordinary
opportunity to advance my training in clinical outcome research, leadership, and iPSC technologies. This
training will equip me with the unique tools and skill sets required to excel as an independent translational
scientific investigator.

## Key facts

- **NIH application ID:** 9916684
- **Project number:** 5K01AG062796-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Chihiro Sato
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $119,326
- **Award type:** 5
- **Project period:** 2019-06-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9916684

## Citation

> US National Institutes of Health, RePORTER application 9916684, Tau Kinetics in the human CNS in vivo and in vitro (5K01AG062796-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9916684. Licensed CC0.

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