Increased regional cerebral glucose uptake in an APP/PS1 model of Alzheimer's disease

Abstract

Alzheimer’s disease (AD), the most common age-related neurodegenerative disorder, is characterized by the invariant cerebral accumulation of β-amyloid peptide. This event occurs early in the disease process. In humans, [18F]-Fluoro-2-deoxy-D-Glucose-Positron Emission Tomography ([18F]-FDG-PET) is largely used to follow-up in vivo cerebral glucose utilisation (CGU) and brain metabolism modifications associated to the AD pathology. Here, [18F]-FDG-PET was used to study age-related changes of CGU under resting conditions in 3, 6 and 12-month-old APPSweLon/PS1M146L, a mouse model of amyloidosis. We showed an age-dependent increase of glucose uptake in several brain regions of APP/PS1 mice but not in control animals and a higher [18F]-FDG uptake in the cortex and the hippocampus of 12-month-old APP/PS1 mice as compared to age-matched control mice. We then developed a method of 3D-microscopic autoradiography to evaluate glucose uptake at the level of amyloid plaques and showed an increased glucose uptake close to the plaques rather than in amyloid-free cerebral tissues. These data suggest a macroscopic and microscopic reorganisation of glucose uptake in relation to cerebral amyloidosis.

Glial Activation and Glucose Metabolism in a Transgenic Amyloid Mouse Model: A Triple-Tracer PET Study

“…Furthermore, normalized 18 F-FDG uptake, a small-animal PET marker for glucose metabolism, was elevated in PS2APP mice, especially in the young group and to a lesser extent still at 16 mo of age, compared with findings in WT groups. This seems in line with previous reports of elevated relative glucose metabolism in amyloid models, such as APP/PS1 (27) and 5xFAD (28) mice, in which glial activation was discussed as a probable factor. However, this interpretation seems at odds with 18 F-FDG findings in human AD and in prodromal patients with amnesic mild cognitive impairment (29).…”

Overexpression of Pyruvate Dehydrogenase Kinase 1 and Lactate Dehydrogenase A in Nerve Cells Confers Resistance to Amyloid β and Other Toxins by Decreasing Mitochondrial Respiration and Reactive Oxygen Species Production

“…In 3-, 6-, and 12-month-old tg-AD mice, it was found that there was an age-dependent increase in glucose uptake in the cortex, hippocampus, and striatum, areas associated with high plaque accumulation (54). However, this study did not discern what proportion of glucose was processed by aerobic glycolysis versus mitochondrial respiration.…”

Hypermetabolic State in the 7-Month-Old Triple Transgenic Mouse Model of Alzheimer'S Disease and the Effect of Lipoic Acid: A 13C-NMR Study

“…The 7-month-old Tg2576 mice show an increased cerebral glucose uptake 27 and the APP/PS1 mouse model revealed increased glucose uptake only close to plaques but not in amyloid-free cerebral tissues 28 and increased basal metabolic rate of cells surrounding amyloid plaques. 29 The 5XFAD mouse model of AD also showed an increased brain glucose uptake.…”