Evidence for high affinity choline transport in synaptosomes prepared from hippocampus and neocortex of patients with Alzheimer's disease.
Sodium-dependent, hemicholinium-sensitive choline transport was measured in purified synaptosomes prepared from fresh necropsy brain of patients with senile dementia of the Alzheimer type and from control subjects. Choline transport velocity was standardized in terms of the occluded lactate dehydrogenase activity of the various synaptosomal preparations, rather than in terms of the protein content, since this enzyme is more representative of the synaptosome content of the purified homogenates. A regional difference in high-affinity choline transport was observed in purified synaptosomes prepared from brains of mentally normal controls; the velocities of sodium-dependent and hemicholinium-sensitive choline uptake into synaptosomes from hippocampus were about twice as great as that into synaptosomes from frontal cortex, indicating a greater relative density of cholinergic innervation in the hippocampus. Hippocampal and neocortical cholinergic nerve cell endings, prepared as synaptosomes, from brains of patients with Alzheimer's disease, also accumulated choline by a high-affinity mechanism; however, the velocity of uptake into both brain areas was decreased in comparison with controls. Choline transport into synaptosomes from Alzheimer frontal cortex was reduced approximately 50%, while uptake into Alzheimer hippocampal synaptosomes represented only 20% of the control activity. The reduction in synaptosomal high-affinity choline transport in Alzheimer's disease could be indicative of degeneration of cholinergic nerve terminal boutons resulting from cholinergic nerve cell death, or could result from an overall decrease in the number of carrier sites per nerve terminal or in the carrier transport velocity.(ABSTRACT TRUNCATED AT 250 WORDS)
D000109:Acetylcholine / Q000378:metabolism; D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D002794:Choline / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D009474:Neurons / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism*
D002794:Choline; D000109:Acetylcholine