Vesicular acetylcholine transporter density and Alzheimer's disease

We have evaluated the vesamicol analogue meta [I-25]iodobrnzyltrozamicol {(+)-[I-125]MIBT} as a probe to assess cholinergic terminal integrity in the human temporal cortex. Saturation binding analysis, using 5-aminobenzovesamicol (ABV) to define nonspecific binding, revealed a high-affinity binding sire with a K-d value of 4.3 +/- 1.2 nM in the temporal cortex of the young control subjects. Similar affinity values were observed for (+)-[I-125]MIBT binding in aged control subjects (K-d = 3.4 +/- 0.5 nM) and AD patients (K-d = 3.0 +/- 0.8 nM). In contrast, Bmax values for young subjects, aged controls and AD patients were 31.2 +/- 6.3, 17.0 +/- 2.0 and 9.4 +/- 1.6 pmol/g, respectively, clearly reflecting significant reductions in (+)-[I-125]MIBT binding site density with aging and age-related neuropathology. Moreover, the decrease in (+)-[I-125]MIBT binding was correlated with choline acetyltransferase activities (r = 0.72) in the AD temporal cortex. These results suggest that when selective ligands are used, the vesicular acetylcholine transporter can be a useful marker protein for assessing the loss of cholinergic projections in AD and related disorders. (C) 1997 Elsevier Science Inc.