Neuron loss from the hippocampus of Alzheimer's disease exceeds extracellular neurofibrillary tangle formation

Neurofibrillary tangle (NFT) formation in the CA1 region of the hippocampus is one of the early events in the pathogenesis of Alzheimer's disease (AD). As the disease progresses more NFTs form and there is substantial neuron loss. In this study we investigated whether NFT formation accounts for all the CA1 pyramidal neuron loss seen in AD. Using unbiased stereological techniques, we estimated the total number of neurons and the number of intra- and extra-cellular NFTs in the hippocampus of 10 patients with AD and 10 age-matched controls. Marked neuronal loss (~60%) was identified in AD, although NFTs accounted for only a small proportion of this loss (2.2–17.2%, mean 8.1%). Analysis of NFT accumulation with duration of dementia showed a linear relationship, supporting the belief that NFTs progressively accumulate with time.