Dysfunctional cerebral glucose transport in Alzheimer’s disease

Abstract

Background: Glucose is the primary energy source required for the homeostatic function of the brain. Glucose transporter 1 (GLUT1) present at the blood-brain barrier is a key regulator of glucose transport into the brain. Reduced GLUT1 expression is shown to exacerbate Alzheimer's pathology in rodent models. Here we aimed to establish whether there are regional differences in ineffective glucose transport amongst people living with Alzheimer's disease. Method(s): 125 participants diagnosed with Alzheimer's dementia, with an [18F]FDG scan with atrial input were enrolled. All participants underwent 3-tesla magnetic resonance imaging and [18F]FDG scan with continuous and discrete arterial sampling. Spectral analysis was performed to create 1-minute input-response function parametric maps. To produce glucose transfer maps we applied the following equation; K1 * Ca / tau (K1 = 1-minute IRF map, Ca = Plasma glucose concentration, tau = 1.48 a lumped constant). Glucose transfer maps were then coregistered to the participants' structural MRI and normalised to MNI space. Regional mean glucose transfer was then calculated for the anterior cingulate cortex, frontal lobe, hippocampus, parahippocampus, occipital lobe, parietal lobe, posterior cingulate cortex, striatum, temporal lobe, and thalamus. A within-subject ANOVA was then performed to evaluate the regional differences in cerebral glucose transport. Result(s): The parahippocampus exhibited the lowest rate of glucose transfer in comparison to all other regions (p < 0.001), followed by the hippocampus. The striatum and occipital lobe demonstrated the regions of the highest mean glucose transportation from blood to the brain. In terms of brain lobes, the temporal lobe showed the lowest rates of glucose transfer, followed by the parietal lobe, then frontal and occipital (p < 0.001). Conclusion(s): We demonstrate dysfunctional BBB glucose transport in Alzheimer's disease, with prominent glucose transport abnormalities localised in the parahippocampus. Impaired glucose transport was most apparent within temporal lobe structures. Targeting glucose transfer may be an effective way of treating Alzheimer's disease.