METABOLIC PROFILING OF ALZHEIMER'S DISEASE
The brain’s demand for energy is disproportionately large for its size, accentuating the importance of robust microvascular function to compensate for the dynamic range of energy demands the neuronal network has for normal brain function. In fact, various forms of neurodegeneration that exhibit progressive decline in brain function can be associated with alterations in microvascular function and metabolism.
At the Functional Brain Imaging Lab (fBIL), we a rat model of Alzheimer’s disease (the TgF344-AD rat: TgAD) to further our understanding of how different aspects of brain function and underlying mechanisms are altered in the most common form of dementia. In particular, emerging evidence in both AD patients and animal models of AD show alterations in metabolic pathways in the presymptomatic stage of AD. Characterizing changes in metabolic pathways prior to manifestation of cognitive deficits in our rat model serves the purpose of identifying early biomarkers of AD and completing our understanding of AD pathology before the onset of clinical symptoms. Our goal is to establish metabolic alterations in the hippocampus and entorhinal cortex of TgAD rats during their presymptomatic disease stage. Here, brain metabolism is assessed by glucose uptake and ketone metabolism using MRI Chemical Exchange Saturation Transfer (CEST) and MR spectroscopy, respectively. Additionally the imaging protocol devised for this study will have methodological contributions to the current array of metabolic imaging methods by enabling repeated scans at higher spatial and temporal resolution.
Estimated glucose uptake in brain using CEST contrast with the preclinical 7T MR system. Presymptomatic TgAD rats show significantly attenuated hippocampal glucose uptake as evident from the short-lived window of uptake compared to non-transgenic (nTg) rats.
Estimation of hippocampal metabolite concentration in presymptomatic TgAD rats. Modelling single-voxel spectroscopy data (black) using a combination of all basis sets (pink; one for each metabolite) enables quantification of metabolite concentration.
