DIFFERENTIAL ALTERATIONS OF ION-CHANNEL BINDING-SITES IN TEMPORAL ANDOCCIPITAL REGIONS OF THE CEREBRAL-CORTEX IN ALZHEIMERS-DISEASE

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: I-12 5-apamin to label a population of Ca2+-sensitive K+ channels; [H-3]PN2 00-110 to label L-type voltage-sensitive Ca2+ channels and [H-3]gliben clamide 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 I -125-apamin binding was increased compared to controls (e.g. superfici al layers: control = 0.71 +/- 0.07; AD = 1.02 +/- 0.07, mean +/- S.E.M . pmol/g tissue). In contrast, in adjacent sections [H-3]glibenclamide binding was reduced in AD compared to controls (e.g. superficial laye rs: control = 25.3 +/- 1.7; AD = 17.9 +/- 1.4 pmol/g tissue). [H-3]PN2 00-110 binding in temporal cortex was not altered in AD compared to co ntrols. In the occipital cortex I-125-apamin binding was increased in AD while both [H-3]glibenclamide and [H-3]PN-200-1 10 binding sites in this cortical area were not different from controls. Plaque density ( per mm2) 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 ChA T activity was reduced by 40% in temporal cortex and by 50% in occipit al cortex compared to controls. The results suggest that the three ion channel binding sites are located on structural elements in the brain which are differentially affected by the pathophysiology of AD.