Wendy Oakden, Canada
Sunnybrook Health Sciences Centre Physcial SciencesAuthor Of 1 Presentation
LOCAL AND GLOBAL METABOLIC IMPAIRMENTS IN PRODROMAL STAGE OF ALZHEIMER’S DISEASE
Abstract
Aims
This work aims to characterize local and global impairments of cerebral metabolism in early stage of Alzheimer’s disease (AD) in terms of glucose uptake and ketone body utilization using a transgenic rat model of AD. Further, this study provides preclinical evidence for clinical use of MR-based imaging protocol for risk assessment of AD in human patients.
Methods
TgF344-AD (TgAD) rat model has been established as an animal model of AD that presents progressive amyloidosis, tauopathy, frank neuronal loss in addition to cognitive decline. Under 1 to 2% isoflurane, 9-month-old TgAD and age-matched homozygous non-transgenic (nTg) rats were studied using the imaging protocol that included multiple post-labeling delay pseudo-continuous arterial spin labeling for resting perfusion and chemical exchange saturation transfer with 2-Deoxy-D-glucose (2DG) injection and proton magnetic spectroscopy for quantification of tissue glucose and β-hydroxybutyrate (BHB) concentration, respectively.
Results
Glucose uptake of TgAD rats following 2DG injection was significantly reduced in cortex, hippocampus, and striatum compared to that of nTg rats. 
While tissue glucose concentration of TgAD rats following overnight fasting was significantly higher than that of the nTg rats, TgAD rats exhibited significantly lower tissue BHB concentration after 2DG injection compared to nTg rats despite having comparable blood BHB concentration.
Conclusions
There is a significant alteration in cerebral metabolism that precedes the onset of AD's clinical symptoms, corroborating the findings in human AD patients. Also, this study demonstrates the potential of MR imaging and spectrocopy as a viable alternative to FDG-PET imaging for longitudinal assessment of cerebral metabolism with improved spatial resolution.