In vivo localized two dimensional MR spectroscopy to compare the neurochemical profile in wild-type and transgenic mouse model of Alzheimer’s disease

Introduction Currently a definitive diagnosis of Alzheimer’s disease (AD) is only possible postmortem, by detecting the two hallmarks of the disease: amyloid plaques and neurofibrillary tangles in the brain tissue. There is thus a great need for in vivo biomarkers to diagnose AD with high specificity and sensitivity. Proton magnetic resonance spectroscopy (H MRS) provides a non-invasive way to investigate in vivo neurochemical abnormalities of many brain disorders. While transgenic mouse models of AD might be instrumental in discovering new in vivo biomarkers, the use of localized in vivo 1D MRS in mice is often hampered by low sensitivity of local measurements due to both the small size of the brain resulting in limited signal-to-noise ratio and low concentrations of several brain metabolites. In addition a considerable overlap of peaks of metabolites with coupled spin systems restricts the number of molecules which can be uniquely assigned in 1D MRS. To overcome the problem of spectral resolution and peak overlap, a two-dimensional (2D) MRS technique has been recently employed at 9.4T to obtain highly resolved localized 2D MR spectra from the living mouse brain. In the present study we employed localized 2D MRS to map the neurochemical composition of a transgenic mouse model of AD and compared it with control mice. Our results show clear differences in the neurometabolic profile of wild-type and transgenic mice.