High-affinity choline uptake carrier in Alzheimer's disease: implications for the cholinergic hypothesis of dementia.
We examined the density and the state of affinity of [3H]hemicholinium-3 ([3H]HC-3) binding sites, a marker of the presynaptic high-affinity choline uptake (HACU) carrier, in 4 representative regions of 13 postmortem Alzheimer's disease (AD) brains, as well as in 12 matched control brains. Significant reductions in the densities of [3H]HC-3 binding sites were found both in frontal cortex (-44.7%) and hippocampus (-36.5%) of AD brains in comparison to controls. On the other hand the densities of [3H]HC-3 binding sites in AD brains in caudate-putamen and cerebellar cortex showed no significant differences when compared to controls. No significant change in the state of affinity of these sites could be observed in the saturation assays carried out in hippocampus and frontal cortex. Our findings concur with the reported data by using other presynaptic cholinergic markers in AD and confirm that some degree of cholinergic degeneration, highly specific for the basal forebrain neurons, occurs in AD. However, these results, obtained in a group of AD brains belonging to severely demented patients, do not show a dramatic loss of the HACU in many AD brains. Although this fact could be due to the existence of a compensatory mechanism, our results probably suggest that dementia in AD cannot be explained only by the loss of neocortical cholinergic presynaptic terminals arising from the basal forebrain and also may clarify as to why the acetylcholine precursors or the muscarinic agonists are not effective in AD dementia.
Pascual
J
J
Department of Physiology and Pharmacology, University of Cantabria, Faculty of Medicine, Santander, Spain.
Fontán
A
A
Zarranz
J J
JJ
Berciano
J
J
Flórez
J
J
Pazos
A
A
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D001665:Binding Sites; D001692:Biological Transport; D001921:Brain / Q000378:metabolism*; D002421:Caudate Nucleus / Q000378:metabolism; D002525:Cerebellar Cortex / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D002794:Choline / Q000378:metabolism*; D005260:Female; D006426:Hemicholinium 3 / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008297:Male; D009928:Organ Specificity; D011699:Putamen / Q000378:metabolism
D006426:Hemicholinium 3; D002794:Choline