Differential alterations of ion channel binding sites in temporal and occipital regions of the cerebral cortex in Alzheimer's disease

Abstract

Three ion channel binding sites were examined by means of quantitative ligand binding autoradiography in temporal and occipital cortex from 9 patients with neuropathologically confirmed Alzheimer's disease (AD) and 7 matched control subjects. The following ligands were used: 125I-apamin to label a population of Ca 2+-sensitive K + channels; [ 3H]PN200-110 to label L-type voltage-sensitive Ca 2+ channels and [ 3H]glibenclamide to label ATP-sensitive K + channels. Ion channel binding sites were compared to: choline acetyltransferase (ChAT) activity and plaque densities measured in the same tissue. In the temporal cortex in AD 125I-apamin binding was increased compared to controls (e.g. superficial layers: control= 0.71 ± 0.07;AD= 1.02 ± 0.07,mean±S.E.M. pmol/g tissue). In contrast, in adjacent sections [ 3H]glibenclamide binding was reduced in AD compared to controls (e.g. superficial layers: control= 25.3 ± 1.7;AD= 17.9 ± 1.4pmol/g tissue). [ 3H]PN200-110 binding in temporal cortex was not altered in AD compared to controls. In the occipital cortex 125I-apamin binding was increased in AD while both [ 3H]glibenclamide and [ 3H]PN-200-110 binding sites in this cortical area were not different from controls. Plaque density (per mm 2) was higher in temporal (e.g. layers I–III, 43 ± 6) than in occipital cortex (layers I–III, 27 ± 4) in the AD patients while ChAT was reduced by 40% in temporal cortex and by 50% in occipital cortex compared to controls. The results suggests that the three ion channel binding sites are located on structural elements in the brain which are differentially affected by the pathophysiology of AD.