Vesicular acetylcholine transporter density and Alzheimer's disease.
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 Kd 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 (Kd = 3.4 +/- 0.5 nM) and AD patients (Kd = 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.
Efange
S M
SM
Department of Radiology, University of Minnesota, Minneapolis 55455, USA.
Garland
E M
EM
Staley
J K
JK
Khare
A B
AB
Mash
D C
DC
D000109:Acetylcholine / Q000032:analysis*; D000328:Adult; D000345:Affinity Labels / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000175:diagnosis / Q000378:metabolism*; D015415:Biomarkers; D002352:Carrier Proteins / Q000032:analysis*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins; D008875:Middle Aged; D010880:Piperidines / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism; D013702:Temporal Lobe / Q000737:chemistry* / Q000378:metabolism; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins
D000345:Affinity Labels; D015415:Biomarkers; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D010880:Piperidines; D011950:Receptors, Cholinergic; C493459:SLC18A3 protein, human; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins; C083232:vesamicol receptor; C006189:vesamicol; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine