# Tau mislocalization assay to screen AD therapeutics using compartmentalized chips

> **NIH NIH R43** · XONA MICROFLUIDICS, LLC · 2022 · $268,419

## Abstract

PROJECT SUMMARY:
Neurofibrillary tangles, a hallmark of Alzheimer's disease (AD), are formed following tau dissociation from
microtubules and mislocalization to the somatodendritic compartment of affected neurons. Pathological tau is
then released from affected neurons and spreads trans-synaptically eventually leading to cell death.
Preventing the initial mislocalization of intracellular tau within the somatodendritic compartment presents an
early therapeutic target and may lead to strategies that limit the progression of AD. Xona Microfluidic, Inc.
(“Xona”) proposes to develop a reliable, reproducible, and scalable screening assay to identify and validate
therapeutic targets that prevent early mislocalization of intracellular tau. The goal of this project is to establish
the feasibility of providing preclinical screening services using this assay for AD and AD-related diseases.
Preliminary data suggests that tau mislocalization can be modeled in Xona's proprietary compartmentalized
microfluidic chips by restricting exposure of Aβ-induced neuroinflammatory media to the axonal compartment.
The resulting tau mislocalization correlates with an increase in synaptic vesicle release, which is consistent
with AD pathophysiology. Xona proposes to develop this screen on the basis of this preliminary data and using
human induced pluripotent stem cell differentiated neurons cultured in 3D, which more closely mimic human
disease phenotypes than murine models. Aim 1 will determine the extent to which 3D cultures improve
synapse maturation over 2D cultures using these neurons within our compartmentalized chips. Aim 2 will
develop a tau mislocalization assay using Aβ-induced neuroinflammatory media. Further, we will evaluate the
reliability and suitability of this assay for drug screening using an established metric of screening potential.
Once feasibility is shown, Xona will focus on forming partnerships with potential customers and scaling up the
number of compounds that can be screened.

## Key facts

- **NIH application ID:** 10384739
- **Project number:** 1R43AG072985-01A1
- **Recipient organization:** XONA MICROFLUIDICS, LLC
- **Principal Investigator:** ANNE MARION TAYLOR
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $268,419
- **Award type:** 1
- **Project period:** 2022-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10384739

## Citation

> US National Institutes of Health, RePORTER application 10384739, Tau mislocalization assay to screen AD therapeutics using compartmentalized chips (1R43AG072985-01A1). Retrieved via AI Analytics 2026-08-03 from https://api.ai-analytics.org/grant/nih/10384739. Licensed CC0.

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