Abstract

[ 3H]PN200-110 binding sites were studied by means of quantitative autoradiography in hippocampal sections of patients with Alzheimer's disease and age-matched control subjects. Choline acetyltransferase activity, plaque, tangle and cell densities were also determined in the same tissue samples used for autoradiographic studies. Quantitative autoradiographic analysis of [ 3H]PN200-110 binding in control hippocampus revealed a heterogeneous pattern similar to that described in rodents, being particularly high in the dentate gyrus. In Alzheimer's disease, [ 3H]PN200-110 binding was markedly reduced in the subiculum (control = 9.85 ± 1.41 pmol/g; Alzheimer = 3.41 ± 0.54 pmol/g, mean ± S.E.M., P < 0.001). In the subiculum there was a disproportionate reduction of [ 3H]PN200-110 binding in comparison to cell loss in Alzheimer's disease. The activity of choline acetyltransferase in the hippocampus was markedly reduced in Alzheimer's disease (controls 6.9 ± 1.0; Alzheimer 2.7 ± 0.9 nmol/h/mg protein, mean ± S.E.M., P < 0.01). There was a strong corrElation between choline acetyltransferase activity and [ 3H]PN200-110 binding in the subiculum. [ 3H]PN200-110 binding did not correlate with plaque density in the subiculum. The discrete reduction and preservation of [ 3H]PN200-110 binding in the present study is consistent with the pattern of selective cellular vulnerability in the hippocampal region in Alzheimer's disease.

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