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.