Longitudinal study of neurochemical, volumetric and behavioral changes in Q140 & BACHD mouse models of Huntingtons disease

Abstract

Brain metabolites, detectable by magnetic resonance spectroscopy (MRS), have been examined as potential biomarkers in Huntingtons Disease (HD). In this study, the RQ140 and BACHD transgenic mouse models of HD were used to investigate the relative sensitivity of the metabolite profiling and the brain volumetry to characterize mouse HD. Magnetic resonance imaging (MRI) and 1H MRS data were acquired at 9.4 T from the transgenic mice and wild-type littermates every 3 months until death. Brain shrinkage was detectable in striatum of both mouse models at 12 months compared to littermates. In Q140 mice, increases in PCr and Gln occurred in striatum prior to cortex. Myo-inositol was significantly elevated in both regions from an early age. Lac, Ala and PE decreased in Q140 striatum. Tau increased in Q140 cortex. Metabolite changes in the BACHD cortex and striatum were minimal with a striatal decrease in Lac being most prominent, consistent with a dearth of ubiquitin and 1C2 positive aggregates detected in those regions. Binary logistical regression models generated from the Q140 metabolite data were able to predict the presence of disease in the BACHD striatal and previously published R6/2 metabolite data. Thus, neurochemical changes precede volume shrinkage and become potential biomarkers for HD mouse models Introduction