Vesicular acetylcholine transporter density and Alzheimer's disease

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

Research output: Contribution to journalArticle

70 Citations (Scopus)

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
Pages (from-to)407-413
Number of pages7
JournalNeurobiology of Aging
Volume18
Issue number4
DOIs
StatePublished - Jul 1 1997

Fingerprint

Vesicular Acetylcholine Transport Proteins
Temporal Lobe
Alzheimer Disease
Cholinergic Agents
Binding Sites
Choline O-Acetyltransferase
Ligands
Proteins

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)

Cite this

Efange, S. M. N., Garland, E. M., Staley, J. K., Khare, A. B., & Mash, D. C. (1997). Vesicular acetylcholine transporter density and Alzheimer's disease. Neurobiology of Aging, 18(4), 407-413. https://doi.org/10.1016/S0197-4580(97)00038-9

Vesicular acetylcholine transporter density and Alzheimer's disease. / Efange, S. M N; Garland, E. M.; Staley, J. K.; Khare, A. B.; Mash, Deborah C.

In: Neurobiology of Aging, Vol. 18, No. 4, 01.07.1997, p. 407-413.

Research output: Contribution to journalArticle

Efange, SMN, Garland, EM, Staley, JK, Khare, AB & Mash, DC 1997, 'Vesicular acetylcholine transporter density and Alzheimer's disease', Neurobiology of Aging, vol. 18, no. 4, pp. 407-413. https://doi.org/10.1016/S0197-4580(97)00038-9
Efange, S. M N ; Garland, E. M. ; Staley, J. K. ; Khare, A. B. ; Mash, Deborah C. / Vesicular acetylcholine transporter density and Alzheimer's disease. In: Neurobiology of Aging. 1997 ; Vol. 18, No. 4. pp. 407-413.
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