# Noninvasive sensory stimulation to promote glymphatic-lymphatic clearance for the treatment of Alzheimer’s Disease

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2024 · $600,077

## Abstract

Alzheimer's disease (AD) is an incurable brain disease, distinguished by the progressive accumulation of toxic
amyloid and tau protein aggregates that are partly due to impaired waste clearance by the glymphatic and
meningeal lymphatic systems. We have recently shown that noninvasive Gamma ENtrainment Using Sensory
stimuli (GENUS) to induce neural oscillations in the gamma frequency range (30-90 Hz) could ameliorate
pathology in various AD mouse models. Mice subjected to GENUS regime exhibited positive effects on microglia,
astrocytes and the brain vasculature as well as reduced accumulation of amyloid and hyperphosphorylated tau
in respective amyloid and tauopathy mouse models. However, the impact of GENUS on the glymphatic/lymphatic
systems in the clearance of amyloid and tau accumulation is not clear. We will use amyloid and tauopathy
mouse models to determine whether and identify the mechanisms by which GENUS enhances paravascular
fluid movement and thereby promotes meningeal lymphatic drainage and glymphatic clearance of brain toxic
metabolites including those associated with amyloid and tau.

## Key facts

- **NIH application ID:** 10837814
- **Project number:** 5R01AT011460-04
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Li-Huei Tsai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $600,077
- **Award type:** 5
- **Project period:** 2021-05-15 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10837814

## Citation

> US National Institutes of Health, RePORTER application 10837814, Noninvasive sensory stimulation to promote glymphatic-lymphatic clearance for the treatment of Alzheimer’s Disease (5R01AT011460-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10837814. Licensed CC0.

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