Vesicular acetylcholine transporter density and Alzheimer's disease

S. M.N. Efange, E. M. Garland, J. K. Staley, A. B. Khare, D. C. Mash

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

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 languageEnglish (US)
Pages (from-to)407-413
Number of pages7
JournalNeurobiology of aging
Volume18
Issue number4
DOIs
StatePublished - 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)

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