# To Study Mechanisms of a Non-Pharmacological Treatment Strategy for Alzheimer’s disease

> **NIH NIH R15** · VIRGINIA COLLEGE OF OSTEOPATHIC MEDICINE · 2021 · $474,750

## Abstract

Project Summary/Abstract: Accumulation of brain derived metabolic waste is the major pathophysiological
feature of Alzheimer’s disease. We hypothesize that brain waste clearance can be accelerated by a
mechanoceutics treatment known as cranial osteopathic manipulation (COM). COM has been successfully used
in the outpatient setting for various neurological disorders and has been proven effective by cross disciplinary
studies. Although in clinical practice since 1930’s, lack of understanding of COM molecular mechanisms limit
public awareness and interest on this non-invasive treatment which has potential to improve the symptoms of
Alzheimer’s disease. Therefore, it is critical to understand the biological effect of COM treatment using
experimental animal models of Alzheimer’s disease. Here, we propose to study the molecular mechanisms of
COM induced improvement in cognitive function, CNS fluid circulation and relevant changes in protein
expression using aged and transgenic rat model of Alzheimer’s disease. In this research work, we will carry out
the following specific aims to understand the mechanisms of COM: Aim 1. To determine the influence of COM
on spatial learning and memory in transgenic and naturally aged rat model of Alzheimer’s disease. Osteopathic
physicians with expertise in COM will, by wearing custom made tactile pressure monitoring nano-sensor gloves,
apply quantifiable mechanical pressure around the fourth ventricle with the goal of improving fluid circulation in
the rat brain. This treatment induced improvement in learning and memory will be studied by two independent
behavioral assays. These experiments will reveal the changes in cognitive function produced by transferring
COM to an experimental animal model of Alzheimer’s disease. Aim 2. To demonstrate COM induced
improvement in brain fluid circulation in live rats. We will study the changes in the kinetics of radioactive tracer
fluorodeoxyglucose movement through cisterna magna, deep cervical lymph nodes and heart using dynamic
positron emission tomography imaging. Further a dynamic contrast-enhanced magnetic resonance imaging will
be performed to study spatiotemporal changes in gadolinium signal intensity to determine solute movement
velocity. These live animal imaging studies will report COM mediated effects in CNS fluid circulation. Aim.3 To
identify molecular level changes in substrates of learning and memory and brain fluid circulation in COM treated
animals. Quantitative immunoassays will be carried out to study the expression of macromolecules including
amyloid and markers of lymphangiogenesis, water homeostasis and synaptic substrates of learning and memory.
Collectively, these findings will provide insights on the molecular mechanism of COM effects observed in aim 1
and 2. Overall, this proposal seeks to study the biology of a medical practice that is not generally considered as
part of conventional medicine. The outcome of this study will generate public awareness and ...

## Key facts

- **NIH application ID:** 10114620
- **Project number:** 1R15AT010789-01A1
- **Recipient organization:** VIRGINIA COLLEGE OF OSTEOPATHIC MEDICINE
- **Principal Investigator:** Blaise Costa
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $474,750
- **Award type:** 1
- **Project period:** 2021-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10114620

## Citation

> US National Institutes of Health, RePORTER application 10114620, To Study Mechanisms of a Non-Pharmacological Treatment Strategy for Alzheimer’s disease (1R15AT010789-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10114620. Licensed CC0.

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