# Interplay of Neuroinflammation and Tau Transport in a Microfluidic Primary Neural Cell Tri-Culture Model

> **NIH NIH R03** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $71,361

## Abstract

PROJECT SUMMARY
Alzheimer’s Disease (AD) is a progressive neurodegenerative brain disorder that impairs memory and cognitive
functions. It is the most common dementia among older adults over age 65 and it is estimated that more than
5.8 million Americans may have dementia caused by AD. While the pathogenesis of AD is unclear, abnormal
deposits of amyloid-β (Aβ) plaques and hyperphosphorylated tau proteins throughout the brain are thought to
play a role in neuroinflammation, synapse loss, and neuronal cell death. While Aβ appears to spread in a diffuse
manner, phosphorylated tau proteins are hypothesized to propagate between synaptically connected neurons.
Recent studies suggest that the presence of Aβ may increase the rate of propagation, potentially due to
neuroinflammatory effects. In addition, neuroinflammation may directly induce or exacerbate Aβ and tau
proteinopathies, thereby worsen neuroinflammation and leading to further loss of synapses and neurons,
creating a vicious cycle that likely promotes disease progression. However, the exact mechanisms that underlie
propagation phosphorylated tau and its interplay with neuroinflammation remain elusive. Distinguishing these
complex factors from each other in vivo, where numerous confounding signals exist, is extremely challenging.
There is, therefore, a need for new methodologies to bridge this gap for revealing the underlying mechanisms
by which transport of aberrant proteins and neuroinflammation accelerate the progression of AD.
In order to address this need, we will employ a microfluidic in vitro platform in combination with a novel tri-culture
(primary neuron, astrocyte, microglia) rat model of neuroinflammation that have been developed as part of the
PIs’ current R03 award. The microfluidic platform consists of two physically distinct culture chambers (e.g.,
primary and secondary), corresponding to proximal and distal anatomic regions interconnected by microchannels
that allow synaptic connectivity between the two cultures. The immediate goal of this administrative supplement
is to study the contribution of glial cells and inflammation to the transport of abnormal tau proteins. Specifically,
we will (i) determine the influence of Aβ and phosphorylated human tau (expressed by transfected neurons) on
neuroinflammation in the tri-culture model, and (ii) employ the microfluidic platform to decouple the influences of
Aβ addition itself and the Aβ-triggered neuroinflammation on tau propagation along the axonal tracts connecting
the two cultures maintained in the primary and secondary chambers. The pilot study described here is expected
to (i) identify the influence of pathogenic conformations Aβ added to the culture and/or human tau expression
by transfected neurons on neuroinflammation, (ii) decouple the influence of pathogenic Aβ itself or its
corresponding neuroinflammatory cytokine profile on propagation of pathogenic tau via axonal tracts, and (iii)
establish the foundation for future mecha...

## Key facts

- **NIH application ID:** 10289580
- **Project number:** 3R03NS118156-01S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Erkin Seker
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $71,361
- **Award type:** 3
- **Project period:** 2021-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10289580

## Citation

> US National Institutes of Health, RePORTER application 10289580, Interplay of Neuroinflammation and Tau Transport in a Microfluidic Primary Neural Cell Tri-Culture Model (3R03NS118156-01S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10289580. Licensed CC0.

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