SELECTIVE CORTICAL DECREASE OF HIGH-AFFINITY CHOLINE UPTAKE CARRIER IN ALZHEIMERS-DISEASE - AN AUTORADIOGRAPHIC STUDY USING H-3 HEMICHOLINIUM-3

H-3-hemicholinium-3 (H-3-HC-3) binding, a marker of the presynaptic hi gh-affinity choline uptake carrier (HACU), was measured by autoradiogr aphy in several brain regions of 17 Alzheimer's disease (AD) patients and of 11 matched controls. A significant decrease in the density of H -3-HC-3 binding sites was found in entorhinal cortex, hippocampus and layers I-III of the frontal cortex. By contrast, in the caudate-putame n the number of H-3-HC-3 binding sites in AD cases was comparable to t hat of control striata. These data concur with previous results using classical presynaptic markers and reflect the loss in the activity of HACU, and, hence, in the synthesis of acetylcholine, that selectively occurs in cortical areas of AD brains due to the degeneration of presy naptic cholinergic terminals arising from the basal forebrain. However , the relatively low mean reduction in HACU in cortical areas (-40%), together with the apparent indemnity of this marker in certain severel y demented AD cases, suggest that AD dementia cannot be explained simp ly by the loss of presynaptic terminals originating in the basal foreb rain. These data seem to be a good explanation for the poor response t o cholinergic replacement in AD.