# Investigation of the role of glia cells in Alzheimers pathogenesis in a functional human-based in vitro model

> **NIH NIH R03** · UNIVERSITY OF CENTRAL FLORIDA · 2021 · $148,185

## Abstract

Scientific Abstract / Summary
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder characterized by progressive
cognitive decline that leads to age-related dementia. The five approved medications provide only modest
symptomatic benefits and provide little effect in halting the disease progression. Improving the mechanistic
understanding of disease onset and progression is essential for developing effective AD drugs. Decades of effort
have focused on “neuron-centric” mechanisms by targeting amyloid beta (Aβ) and Tau pathologies. Recently
neuroinflammation has gained increasing recognition as being an active component in AD etiology. It is
becoming crucial to decipher the activation mechanism of astrocytes and microglia, the major players in CNS
neuroinflammation, and their interactions with neurons during AD pathology. However, the mechanisms of glial
activation and their interplay with neurons is poorly understood, especially in humans, due to the lack of proper
models. This study endeavors to develop a human-based functional system that enables the mechanistic study
concerning neuron-glia interactions, by taking the advantage of the progress made in induced pluripotent stem
cell (iPSC) and Bio-MEMs (microelectromechanical systems) technology. The Specific Aims are: 1) Investigate
the functional deficits of cortical neurons derived from AD patients on patterned MEAs, by quantifying
the amplitude and maintenance of induced long term potentiation (LTP) and the number of functional
synapses, compared to cortical neurons derived from healthy subjects. The longitudinal progression of the
phenotype will also be analyzed. Integration of AD-cortical neurons expressing a familial AD gene could uncover
the autologous functional phenotype in these neurons. 2) Develop a human-based tri-culture model
consisting of human iPSC-derived cortical neurons, astrocytes and microglia, to investigate the neuron-
glia interaction in AD. Both the effect of glial cells on the functionality of AD-neurons and the activation status
of glia in the tri-culture will be examined. The results will help clarify whether astrocytes and microglia are still
protective in the presence of AD-neurons, or becoming toxic at a certain point during the pathological process.
The iPSC-sourced feature enables the possibility of patient-specific modeling. The non-invasive MEA system
allows chronological monitoring of neural circuit function which is critical to investigate aging-related diseases.
Functional readouts, long-term potentiation (LTP) and synapse number have been shown to imitate some clinical
cognitive deficits. The model provides an ideal platform for investigating the early pathology and progression of
functional impairment of AD-neurons and their interactions with glia. Application of this model could uncover
essential mechanisms of glial activation, their interaction with neurons, and reveal potential therapeutic targets
for AD. Both the platform and the etio...

## Key facts

- **NIH application ID:** 10110392
- **Project number:** 1R03AG070514-01
- **Recipient organization:** UNIVERSITY OF CENTRAL FLORIDA
- **Principal Investigator:** Xiufang Guo
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $148,185
- **Award type:** 1
- **Project period:** 2021-01-15 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10110392

## Citation

> US National Institutes of Health, RePORTER application 10110392, Investigation of the role of glia cells in Alzheimers pathogenesis in a functional human-based in vitro model (1R03AG070514-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10110392. Licensed CC0.

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