Neurofibrillary Tangles in Nondemented Elderly Subjects and Mild Alzheimer Disease

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Abstract
A CRITICAL question in understanding the classic neuropathological features of Alzheimer disease (AD) (neuritic plaques [NPs] and neurofibrillary tangles [NFTs])1-3 is whether they precede, follow, or occur in synchrony with the earliest and mildest signs of cognitive deterioration. Although the commonly used formal neuropathological diagnostic criteria for AD rely almost exclusively on the density of neocortical NPs,4,5 several studies6-9 have argued that the development of NFTs, especially in the entorhinal cortex, represents the earliest neuropathological change in AD. In fact, a recent consensus recommendation for the neuropathological diagnosis of AD10 has advised that in addition to the evaluation of NPs, the density and distribution of NFTs be considered in establishing a diagnosis of AD.