MICEST: A potential tool for non-invasive detection of molecular changes in Alzheimer's disease

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.

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► We image the changes in myo-inositol at high spatial resolution in mouse model of Alzheimer's disease.
► This method provides over two orders of magnitude higher sensitivity compared to 1H MRS.
► Glial cells proliferation/activation in Alzheimer's disease can be monitored in vivo noninvasively.
► It has potential for investigating the changes in myo-inositol level at early stage of AD.
► It can be used as a new imaging biomarker in early diagnosis of AD at the stage of mild cognitive impairments.