Tracking the decline in cerebral glucose metabolism in persons and laboratory animals at genetic risk for Alzheimer's disease

Brain imaging methods can be used to track declines in the cerebral metabolic rate for glucose (CMRgl) in the absence of symptoms in persons and laboratory animals at risk for Alzheimer's disease (AD). In fluorodeoxyglucose (FDG) positron emission tomography studies, late middle-aged, cognitively normal carriers of a common Alzheimer's susceptibility gene (the apolipoprotein E ε4 allele) had progressively reduced CMRgl in the same regions of the brain as patients with Alzheimer's dementia. In an FDG autoradiography study, transgenic mice carrying two copies of an Alzheimer's gene (a mutation in the amyloid precursor protein gene) had a similar CMRgl pattern, including progressively reduced CMRgl in the posterior cingulate cortex. Functional brain imaging techniques could be used to help bridge the gap between studies of patients with Alzheimer's dementia, cognitively normal persons at genetic risk for AD, and suitable laboratory animals. By providing a potential indicator of AD, these techniques could help clarify disease mechanisms and screen candidate treatments in at least some transgenic mice, and they could efficiently test the potential of candidate Alzheimer's prevention therapies in persons at genetic risk for the disorder.