# Modulating blood flow and metabolism in Alzheimer's Disease models

> **NIH NIH R21** · NORTHEASTERN UNIVERSITY · 2024 · $200,000

## Abstract

ABSTRACT
This project will develop and apply new intravital microscopy techniques to gain greater insight into the putative
benefits effects of gamma entrainment, a promising nonpharmacological neuromodulation technique for
Alzheimer’s disease (AD) and other brain pathologies. Investigators recently demonstrated the powerful effects
of neuromodulation strategies for preserving synchronized neuronal activity in circuit pathways between the
visual cortex, hippocampus, and pre-frontal cortex. Gamma entrainment using sensory stimulus (GENUS) is a
simple, noninvasive gamma entrainment technique involving repeated exposure to a 40 Hz visual or auditory
stimulus. This method is easily translatable, and remarkably, experiments in preclinical animal models show that
it effectively reduces Amyloid levels and synaptic degradation while evoking morphological changes and cytokine
secretion from microglia. In some human patients, the technique has shown promise for reducing cognitive
decline. Ostensibly, the stimulus parameters require optimization to improve its efficacy in AD patients. The goal
of this project is to gain a deeper understanding of how GENUS influences cerebral energy metabolism and
microvascular hemodynamics. Advanced microscopy methods will be developed and applied to mouse models
of AD to nondisruptively characterize GENUS-related changes to cellular signaling, metabolism, and
microvascular blood flow in the living brain with cellular resolution. By developing new microscopy techniques,
we will explore how these indicators of metabolism and cerebral blood flow change in different regions of the
brain in response to GENUS neuromodulation. The project’s findings will improve our understanding of the
technique’s operating mechanisms. By understanding how GENUS affects measurable changes of brain
hemodynamics, the results will eventually guide strategies to optimize its utility in human patients. Ultimately,
the project’s findings will facilitate development of accessible, nonpharmacological methods to stem AD’s
dramatically increasing global prevalence.

## Key facts

- **NIH application ID:** 10807670
- **Project number:** 1R21AG085655-01
- **Recipient organization:** NORTHEASTERN UNIVERSITY
- **Principal Investigator:** Mohammad Abbas Yaseen
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $200,000
- **Award type:** 1
- **Project period:** 2024-09-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10807670

## Citation

> US National Institutes of Health, RePORTER application 10807670, Modulating blood flow and metabolism in Alzheimer's Disease models (1R21AG085655-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10807670. Licensed CC0.

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