# Gamma Induction for Amyloid Clearance in Alzheimer’s Disease

> **NIH NIH R01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2020 · $630,539

## Abstract

Project Summary
Thanks to advances in public health and medicine, the life expectancy of the world population
continues to lengthen. While longer lifespan is a unique opportunity for society to benefit from
the wisdom and experience of the elderly, aging is however also the greatest risk factor for
neurodegenerative disorders such as Alzheimer's disease (AD). A fundamental neurobiological
substrate of cognitive decline and neurodegeneration appears to involve alteration of
neuroinflammatory processes with associated deposition of aberrant proteins, such as amyloid-
β (Aβ) and phosphorylated tau (p-tau). Recent pre-clinical work from MIT's Li-Huei Tsai, Ed
Boyden and collaborators reveals that induction of gamma oscillations in mice can modulate
activity of microglia, modify inflammatory brain processes, and lead to clearance of Aβ and p-tau
deposition. Translation of such findings to humans could have transformative impact. In recent
years, transcranial Alternating Current Stimulation (tACS) has been shown effective in
modulating brain activity and cortical rhythmic activity by means of low-amplitude alternating
(sinusoidal) currents applied transcranially. In humans, work at the Berenson-Allen (BA) Center
and elsewhere reveals that tACS can be applied safely if appropriate guidelines are followed,
and that when applied at the appropriate alternating frequency it is possible to entrain gamma
oscillations and enhance cognition. Furthermore, repeated sessions of tACS on consecutive
days are safe and lead to an additive effect with longer lasting neuromodulatory impact on brain
oscillation. Given the potential for gamma entrainment in humans via tACS, we propose a first-
to-human translation of the preclinical data on the effect of induction of gamma oscillations on
Aβ and p-tau in patients with mild to moderate AD, leveraging the close collaboration with
Georges El Fakhri, director of the Gordon Center for medical imaging at MGH. Our central
hypothesis is that repeated daily sessions of gamma-tACS in patients with AD will significantly
decrease Aβ plaques and p-tau deposition in neurofibrillary tangles as measured by PET
imaging. This will be correlated with changes on electrophysiological (EEG) measures of brain
function, and on cognitive testing. This pilot study will provide the critical first step in the
development of a novel intervention to prevent and treat AD, demonstrating the potential
mechanisms of action, establishing a dose response relation, and informing the design of an
eventual clinical trial.

## Key facts

- **NIH application ID:** 9852943
- **Project number:** 5R01AG060981-02
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Emiliano Santarnecchi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $630,539
- **Award type:** 5
- **Project period:** 2019-02-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9852943

## Citation

> US National Institutes of Health, RePORTER application 9852943, Gamma Induction for Amyloid Clearance in Alzheimer’s Disease (5R01AG060981-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9852943. Licensed CC0.

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