Scott A. Small
As we age, all of us will experience an inexorable slide into forgetfulness. Age-related memory decline localizes, in part, to the hippocampal formation, a brain circuit made up of separate but interconnected hippocampal subregions. Human studies have established that Alzheimer's disease targets the hippocampal circuit early in its course, and since Alzheimer's disease affects older individuals it is one cause of age-related hippocampal dysfunction. Animal studies, however, have established that the aging process itself targets the hippocampal circuit, contributing to age-related hippo-campal dysfunction observed in all mammalian species. These independent observations have led to a continued debate among investigators of the aging human brain, summarized by the following questions: Is age-related hippocampal dysfunction in humans etiologically homogeneous, or is age-related hippocampal dysfunction caused by both AD and by normal aging? If age-related hippocampal dysfunction is caused by both AD and normal aging how can they be distinguished from each other? If age-related hippocampal dysfunction is caused by both AD and normal aging what are the molecular underpinnings of each? This chapter will review a series of recent studies that rely on in vivo imaging, the results of which have begun addressing these important questions.
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