# Alzheimer's Disease Supplement for Virtual Neuroprosthesis

> **NIH NIH R01** · FLORIDA ATLANTIC UNIVERSITY · 2020 · $349,939

## Abstract

Project Summary/Abstract
 This supplementary research proposal applies the expertise, techniques and hardware developed under the
funded parent grant (R01EB025819) to study the contribution of neuronal activity to the pathogenesis of
Alzheimer’s disease (AD). AD is a progressive multifactorial neurodegenerative disorder and the major type of
dementia. Neuronal activity shows a complex relationship with AD, with (1) neurons and areas susceptible to
more intense neuronal activity, clinically hyper-excitable or stimulated intensely exhibiting evidence of AD
pathogeny in humans, animal models and cell cultures; and (2) neurons or synapses whose activity is reduced
or putatively under-stimulated by lack of cognitive engagement also demonstrating altered prospects as the
disease progresses. Since neuroinflammation is one of the central mechanisms in AD pathogenesis and an area
currently under intensive research, elucidation of its systemic drivers at the neuronal level and pathogenic impact
will provide mechanistic insights on disease progression and uncover intervention principles. We hypothesize
that one of key mediators of this nonlinear relationship between neuronal activity and AD is neuroinflammation,
because studies independently linked neuroinflammation to both sides of the hypothetical equation
AD=f(neuronal activity). Specifically in this application, using an Alzheimer’s-in-a-dish model with neurons-
microglia cocultures derived from induced pluripotent stem cells (iPSCs) of AD patients, we aim to determine the
electrical parameters that modulate neuroinflammatory response and how this relates to AD progression. Our
operational hypothesis is that different patterns of electrical stimulation will nonlinearly affect neuroinflammatory
responses in AD neuron-microglia co-cultures, which in turn contributes to the pathogenesis of AD at the neurons’
structural and functional levels. To test this hypothesis, we propose to deliver different patterns of electrical
stimulation to Alzheimer’s-in-a-dish models and measure cytokine release using cytokine array (Exp. 1), analyze
microglia migration behavior with impedimetric monitoring (Exp. 2) and investigate neuronal function
electrophysiologically with multielectrode array (MEA) (Exp. 3). This plan is executed by an interdisciplinary team
of 4 principle investigators whose skills cover broadly the needs of the research plan, including an expert in the
molecular biology of neurodegeneration/regeneration, a roboticist expert in control systems; a biosensor and
microfluidic nanoengineer and a complexity neuroscientist expert in electrophysiological spatiotemporal
dynamics. This supplement grant is directly focused on investigating AD pathogenesis in the presence of
different neuronal stimulation patterns, which resemble physiological or pathological neuroelectric events
responding to environmental sources. Our proposed studies, thus well aligned with Milestone 2H outlined in the
research implementation pl...

## Key facts

- **NIH application ID:** 10123595
- **Project number:** 3R01EB025819-04S1
- **Recipient organization:** FLORIDA ATLANTIC UNIVERSITY
- **Principal Investigator:** E Du
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $349,939
- **Award type:** 3
- **Project period:** 2017-09-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123595

## Citation

> US National Institutes of Health, RePORTER application 10123595, Alzheimer's Disease Supplement for Virtual Neuroprosthesis (3R01EB025819-04S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10123595. Licensed CC0.

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