¹H- and ¹³C-NMR spectroscopy of Thy-1-APPSL mice brain extracts indicates metabolic changes in Alzheimer's disease
Abstract
Biochemical alterations underlying the symptoms and pathomechanisms of Alzheimer's disease (AD) are not fully understood. However, alterations of glucose metabolism and mitochondrial dysfunction certainly play an important role. (1)H- and (13)C-NMR spectroscopy exhibits promising results in providing information about those alterations in vivo in patients and animals, especially regarding the mitochondrial tricarboxylic acid (TCA) cycle. Accordingly, transgenic mice expressing mutant human amyloid precursor protein (APP(SL))-serving as a model of neuropathological changes in AD-were examined with in vitro 1D (1)H- and 2D (1)H-(13)C-HSQC-NMR spectroscopy after oral administration of 1-(13)C-glucose and acquisition of brain material after 30 min. Perchloric acid extracts were measured using a 500 MHz spectrometer, providing more detailed information compared to in vivo spectra achievable nowadays. Area under curve (AUC) data of metabolite peaks were obtained and normalized in relation to the creatine signal, serving as internal reference. Besides confirming well-known metabolic alterations in AD like decreased N-acetylaspartate (NAA)/Creatine (Cr) ratio, new findings such as a decrease in phosphorylcholine (PC) are presented. Glu...Continue Reading
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