Abstract
We have evaluated the vesamicol analogue meta-[125I]iodobenzyltrozamicol {(+)-[125I]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 site 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 (+-)-[125I]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 (+)-[125I]MIBT binding site density with aging and age-related neuropathology. Moreover, the decrease in (+)-[125I]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.
Original language | English (US) |
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Pages (from-to) | 407-413 |
Number of pages | 7 |
Journal | Neurobiology of aging |
Volume | 18 |
Issue number | 4 |
DOIs | |
State | Published - Jul 1997 |
Keywords
- (+)-Meta-[I]iodobenzyltrozamicol
- Aging
- Alzheimer's disease
- Cholinergic innervation
- Radioligands
- Transporter
- Vesamicol
- Vesamicol receptor
- Vesicular acetylcholine
ASJC Scopus subject areas
- Clinical Neurology
- Biological Psychiatry
- Developmental Neuroscience
- Neurology
- Psychology(all)