# Development of an innovative Non-Invasive MR Imaging Technique for assessing Membrane Lipids and Their Properties in Alzheimer's Disease

> **NIH NIH R21** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $481,250

## Abstract

PROJECT SUMMARY
Phospholipids, the fundamental components of cell membranes, play a crucial role in brain function. Research
indicates that changes in membrane lipid composition and fluidity may be contributing to the development of
Alzheimer’s disease (AD). By studying the distribution and alteration of membrane lipids in response to Aβ
exposure, new insights into the biology of AD and potential biomarkers for the disease may be uncovered.
Despite numerous studies on the role of membrane lipids in AD, research has been restricted to ex-vivo
tissues, and has not been utilized for diagnosis due to the absence of non-invasive imaging techniques. This
project aims to bridge this gap by developing an innovative MRI imaging technique to assess membrane lipid
properties in AD. The technique uses a nuclear Overhauser enhancement (NOE) saturation transfer method.
Our preliminary studies strongly suggest that the NOE signal primarily originates from phospholipids and
changes significantly in AD on animal models. The NOE signal relies on both the underlying pool concentration
and the NOE coupling rate. Moreover, according to NOE theory, the NOE coupling rate depends on the
molecular motional properties, which may serve as an indicator of lipid fluidity as they likely share similar
physical properties. Based on these preliminary findings and analysis, we hypothesize that the NOE pool
concentration could reflect membrane lipid content, and the NOE coupling rate could represent lipid fluidity
regulated by membrane composition. The project is divided into three aims: 1) verifying the dependency of the
NOE signal on lipid properties on reconstituted phospholipid samples and cultured cells with varied lipid
composition; 2) confirming the origin of the NOE imaging in AD by correlating it with phospholipid species
maps determined by imaging mass spectrometry on animal AD models; and 3) evaluating the potential of NOE
for early detection of AD by comparing it with other traditional imaging methods in a longitudinal study. The
ultimate goal of this project is to provide a groundbreaking tool for AD research and diagnosis, enabling the
non-invasive study of membrane lipids in live brains. This could significantly improve our understanding of AD
pathology, potentially leading to new treatment strategies and early diagnosis.

## Key facts

- **NIH application ID:** 10985343
- **Project number:** 1R21AG089699-01
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Zhongliang Zu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $481,250
- **Award type:** 1
- **Project period:** 2024-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10985343

## Citation

> US National Institutes of Health, RePORTER application 10985343, Development of an innovative Non-Invasive MR Imaging Technique for assessing Membrane Lipids and Their Properties in Alzheimer's Disease (1R21AG089699-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10985343. Licensed CC0.

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