engleski

Tau phosphorylation and selective neuronal vulnerability in Alzheimer's disease

The purpose of this study was to quantify the extent of early and late neurofibrillary changes and neuron loss in brains of subjects with sporadic Alzheimer’ s disease (AD) and cognitively intact elderly controls. The neuron loss related to normal aging was evaluated stereologically by optical disector estimates of the total number of neurons in each of the major hippocampal subdivisions of 30 normal subjects aged 16 to 99 years. The AD related losses were evaluated from data obtained from Nissl-stained sections of 25 cases of AD and 22 age matched controls. The number of neurons containing early (immunocytochemistry using AT8 Mab against phosphorylated Ser202/Thr205 of tau) and late (modified Bielschowsky stain according to Yamamoto and Hirano) neurofibrillary pathology was determined in 12 AD and 12 control subjects. Entorhinal and temporal cortices were analyzed in a semiquantitative way. Considering only the data obtained by silver staining, neuron loss in AD subjects in hippocampus and entorhinal cortex largely exceeded the number of neurofibrillary tangles (except in CA1). However, AT8-immunoreactive neurons with initial neurofibrillary changes, which cannot be readily seen by silver stainings, were added to the counts of NFTs, a significantly higher proportions of the neuron loss could be "explained" by the neurofibrillary pathology (except in the granule cell layer). The difference in obtained ratios of stereologic estimates was highest in CA4 (approx. 3.5 neurons per tangle were lost), followed by CA2/3 (1.7), subiculum (0.9) and CA1 field (0.5). These results suggest the existence of distinct topographic and cytochemical determinants of neuronal vulnerability in AD.

tau phosphorylation; neurofibrillary tangles; Alzheimer's disease

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