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 |
|---|---|
| Pages (from-to) | 407-413 |
| Number of pages | 7 |
| Journal | Neurobiology of Aging |
| Volume | 18 |
| Issue number | 4 |
| DOIs | |
| State | Published - Jul 1 1997 |
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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
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 journal › Article
}
TY - JOUR
T1 - Vesicular acetylcholine transporter density and Alzheimer's disease
AU - Efange, S. M N
AU - Garland, E. M.
AU - Staley, J. K.
AU - Khare, A. B.
AU - Mash, Deborah C
PY - 1997/7/1
Y1 - 1997/7/1
N2 - 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.
AB - 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.
KW - (+)-Meta-[I]iodobenzyltrozamicol
KW - Aging
KW - Alzheimer's disease
KW - Cholinergic innervation
KW - Radioligands
KW - Transporter
KW - Vesamicol
KW - Vesamicol receptor
KW - Vesicular acetylcholine
UR - http://www.scopus.com/inward/record.url?scp=0030770648&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030770648&partnerID=8YFLogxK
U2 - 10.1016/S0197-4580(97)00038-9
DO - 10.1016/S0197-4580(97)00038-9
M3 - Article
C2 - 9330972
AN - SCOPUS:0030770648
VL - 18
SP - 407
EP - 413
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
IS - 4
ER -