# Extracranial Brain Stimulation Reduces Metabolic Insufficiency Through Enhanced Cerebral Blood Flow in CVN-AD Alzheimer's Model

> **NIH NIH R01** · DUKE UNIVERSITY · 2024 · $362,250

## Abstract

Alzheimer's disease is a progressive degenerative disorder of unclear etiology and disease-modifying
treatments remain elusive. However, there are abnormalities in substrate delivery to the brain, altered capillary
reactivity, neurovascular coupling, and hemodynamic responsiveness to metabolic stress, such as low glucose
or spreading depression, in both the disease and animal models (CVN-AD). Our hypothesis is that
transcranial alternating current electrical stimulation (tACS) can improve metabolic insufficiency in a
dose dependent and dynamic manner in the CVN-AD animal model of Alzheimer's disease, modulating
disease progression and degeneration.
We will apply tACS through skull mounted electrodes first on a scheduled approach, comparing 10 and 40 Hz
stimulation to enhance cerebral blood flow and improve substrate delivery to the brain, assisted by Dr.'s
Peterchev and Schmidt. Further, we will test behavioral outcomes to assess the effects of chronic, scheduled
tACS and sham tACS over 4 weeks, starting at the critical points of degeneration at 12 and 24 weeks of age in
the CVN-AD model, assessing outcome with probe trial errors on a Barnes maze, cerebral blood flow,
measures of neurodegeneration. As a second goal we will develop dynamic, metabolic need-based tACS,
using closed loop approaches. Surrogate physiological markers will include electrical recordings, glucose
recordings, and EEG signals of activity to augment blood flow in a dynamic manner to improve immediate
metabolic substrate supply and reduce degeneration.
These experiments will establish the feasibility and parameters to translate into initial human studies
using either semi-permanent skull mounted or temporary skin electrodes. Since current density and
intracranial penetration of tACS is limited in humans various translational strategies will be devised to
include dynamic biomarkers and appropriate stimulation levels through subcutaneous electrodes.

## Key facts

- **NIH application ID:** 10771976
- **Project number:** 5R01AG074999-03
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** DENNIS Alan TURNER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $362,250
- **Award type:** 5
- **Project period:** 2022-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10771976

## Citation

> US National Institutes of Health, RePORTER application 10771976, Extracranial Brain Stimulation Reduces Metabolic Insufficiency Through Enhanced Cerebral Blood Flow in CVN-AD Alzheimer's Model (5R01AG074999-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10771976. Licensed CC0.

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