Affiliations: [a] Ecole Polytechnique Fédérale de Lausanne, Laboratory of Functional and Metabolic Imaging (LIFMET), Lausanne, Switzerland | [b] Ecole Polytechnique Fédérale de Lausanne, Brain Mind Institute, Lausanne, Switzerland
Correspondence:
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Correspondence to: Vladimír Mlynárik, PhD, Laboratory of Functional and Metabolic Imaging, Station 6, 1015 Lausanne, Switzerland. Tel.: +41 21 6937685; Fax: +41 21 6937960; E-mail: vladimir.mlynarik@epfl.ch.
Abstract: The development of new diagnostic criteria for Alzheimer's disease (AD) requires new in vivo markers reflecting early pathological changes in the brain of patients. Magnetic resonance (MR) spectroscopy has been shown to provide useful information about the biochemical changes occurring in AD brain in vivo. The development of numerous transgenic mouse models of AD has facilitated the evaluation of early biomarkers, allowing researchers to perform longitudinal studies starting before the onset of the pathology. In addition, the recent development of high-field animal scanners enables the measurement of brain metabolites that cannot be reliably quantified at lower magnetic fields. In this report, we studied a new transgenic mouse model of AD, the 5xFAD model, by in vivo proton and phosphorus MR spectroscopy. This model, which is characterized by an early-onset and a robust amyloid pathology, developed changes in the neurochemical profile, which are typical in the human disease, i.e., an increase in myo-inositol and a decrease in N-acetylaspartate concentrations, as early as in the 40th week of age. In addition, a significant decrease in the γ-aminobutyrate concentration was observed in transgenic mice at this age compared to controls. The pseudo-first-order rate constant of the creatine kinase reaction as well as relative concentrations of phosphorus-containing metabolites were not changed significantly in the 36 and 72-week old transgenic mice. Overall, these results suggest that mitochondrial activity in the 5 × FAD mice is not substantially affected but that the model is relevant for studying early biomarkers of AD.
Keywords: 5xFAD, Alzheimer's disease, in vivo NMR spectroscopy, metabolic profile, transgenic mice
