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Published on: May 3, 2017
MICEST: a potential tool for non-invasive detection of molecular changes in Alzheimer's disease
Mohammad Haris1, Anup Singh, Kejia Cai
1CMROI, Department of Radiology, University of Pennsylvania, Philadelphia, USA. mharis@mail.med.upenn.edu
Abstract:
Myo-inositol (mIns) is a marker of glial cells proliferation and has been shown to increase in early Alzheimer's disease (AD) pathology. mIns exhibits a concentration dependent chemical-exchange-saturation-transfer (CEST) effect (MICEST) between its hydroxyl groups and bulk water protons. Using the endogenous MICEST technique brain mIns concentration and glial cells proliferation can be mapped at high spatial resolution. The high resolution mapping of mIns was performed using MICEST technique on ∼20 months old APP-PS1 transgenic mouse model of AD as well as on age matched wild type (WT) control (n=5). The APP-PS1 mice show ∼50% higher MICEST contrast than WT control with concomitant increase in mIns concentration as measured through proton spectroscopy. Immunostaining against glial-fibric-acidic protein also depicts proliferative glial cells in larger extent in APP-PS1 than WT mice, which correspond to the higher mIns concentration. Potential significance of MICEST in early detection of AD pathology is discussed in detail.
Insights
Myo-inositol (mIns), a marker of glial cell proliferation, increases in early Alzheimer's disease (AD). The MICEST MRI technique effectively maps elevated mIns in AD mouse models, aiding early AD detection.
Area of Science:
- Neuroscience
- Biochemistry
- Medical Imaging
Background:
- Myo-inositol (mIns) is a marker for glial cell proliferation.
- Elevated mIns levels are observed in early Alzheimer's disease (AD) pathology.
- mIns exhibits a concentration-dependent chemical-exchange-saturation-transfer (CEST) effect (MICEST).
Purpose of the Study:
- To map brain mIns concentration and glial cell proliferation at high spatial resolution using endogenous MICEST.
- To investigate the utility of MICEST in detecting early AD pathology.
Main Methods:
- High-resolution mapping of mIns using MICEST technique.
- Utilized APP-PS1 transgenic mouse model of AD and age-matched wild-type (WT) controls.
- Correlated MICEST contrast with proton spectroscopy and glial fibrillary acidic protein (GFAP) immunostaining.
Main Results:
- APP-PS1 mice exhibited approximately 50% higher MICEST contrast compared to WT controls.
- Increased mIns concentration was confirmed in APP-PS1 mice via proton spectroscopy.
- GFAP immunostaining showed more extensive glial cell proliferation in APP-PS1 mice, correlating with higher mIns levels.
Conclusions:
- The MICEST technique allows for high-resolution mapping of endogenous mIns.
- Elevated mIns and glial proliferation are detectable in an AD mouse model using MICEST.
- MICEST shows significant potential for the early detection of AD pathology.
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