# Gamma Induction for Amyloid Clearance in Alzheimer's Disease

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $224,238

## 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 associated with AD appears to involve
alteration of neuroinflammatory processes and inhibitory interneurons’ activity associated with
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, a growing body of literature has shown how 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 for up to 70 minutes after the end of a single stimulation
session 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, the parent R01 award
issued in 2018 is supporting a clinical trial investigating the impact of tACS on gamma oscillatory
activity, as well as its effect on Aβ and p-tau clearance and cognition. The present administrative
supplement will support the upgrade of our originally proposed solutions for monitoring
of gamma activity, via an improved electroencephalography device, a transcranial magnetic
stimulation platform for investigation of inhibitory and excitatory cortical circuitry, and a
neuronavigation suite for accurate tracking of the biophysical impact of tACS on brain structures.

## Key facts

- **NIH application ID:** 10617969
- **Project number:** 3R01AG060981-04S1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Emiliano Santarnecchi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $224,238
- **Award type:** 3
- **Project period:** 2021-12-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10617969

## Citation

> US National Institutes of Health, RePORTER application 10617969, Gamma Induction for Amyloid Clearance in Alzheimer's Disease (3R01AG060981-04S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10617969. Licensed CC0.

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