Loss of dopamine uptake sites labeled with [3H]GBR-12935 in Alzheimer's disease.
The binding of the dopamine uptake inhibitor [3H]GBR-12935 to postmortem putamen from a control group and patients with Alzheimer's disease/senile dementia of Alzheimer type (AD/SDAT) or vascular dementia (VD) was studied. The binding density (Bmax) in AD/SDAT was significantly reduced to 50% of control. A reduction of Bmax in VD was also noted, but it did not reach statistical significance. No differences in apparent binding affinity (Kd) between controls and dementia groups were obtained. The concentrations of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT) and homovanillic acid were also determined. The concentrations of DA and DOPAC were reduced by 30-40% in AD/SDAT and VD, but the reductions did not reach statistical significance. The concentration of 3-MT was reduced by 40% in AD/SDAT and by 30% in VD. The [3H]GBR-12935-binding densities correlated significantly with corresponding concentrations of DA in control brains. It is suggested that the loss of [3H]GBR-12935-binding sites in human putamen in AD/SDAT reflects a degeneration of dopamine neurites.
Department of Geriatric Medicine, University of Umeå, Sweden.
P
P
Allard
I
I
Alafuzoff
A
A
Carlsson
K
K
Eriksson
E
E
Ericson
C G
CG
Gottfries
J O
JO
Marcusson
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008024:Ligands; D008297:Male; D008781:Methyltyrosines / Q000378:metabolism; D008875:Middle Aged; D010879:Piperazines; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism*; D019805:alpha-Methyltyrosine
D008024:Ligands; D008781:Methyltyrosines; D010879:Piperazines; D011954:Receptors, Dopamine; D019805:alpha-Methyltyrosine; C044630:1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine; D004298:Dopamine; D006719:Homovanillic Acid