Alzheimer's disease (AD) is a progressive age-related neurodegenerative disease. Although neurofibrillary tangles and amyloid beta are classic hallmarks of AD, the earliest deficits in AD progression may be caused by unknown factors. One suspected factor has to do with brain energy metabolism. To investigate this factor, brain metabolic activity in 3xTg-AD mice and age-matched controls were measured with FDG-PET. Significant hypometabolic changes (p < .01) in brain metabolism were detected in the cortical piriform and insular regions of AD brains relative to controls. These regions are associated with olfaction, which is a potential clinical marker for AD progression as well as neurogenesis. The activity of the terminal component of the mitochondrial respiratory chain (complex IV) and the expression of complex I-V were significantly decreased (p < .05), suggesting that impaired metabolic activity coupled with impaired oxidative phosphorylation leads to decreased mitochondrial bioenergetics and subsequent Neurodegeneration. Although there is an association between neuroinflammatory pathological markers (microglial) and hypometabolism in AD, there was no association found between neuropathological (Aβ, tau, and astrocytes) and functional changes in AD sensitive brain regions, also suggesting that brain hypometabolism occurs prior to AD pathology. Therefore, targeting metabolic mechanisms in cortical piriform and insular regions at early stages may be a promising approach for preventing, slowing, and/or blocking the onset of AD and preserving neurogenesis.
Keywords: Alzheimer's disease, 3xTg-AD, neurofibrillary tangles; Amyloid beta; FDG-PET; Insular; Pirifom.
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