Monoamine vesicular uptake sites in patients with Parkinson's disease and Alzheimer's disease, as measured by tritiated dihydrotetrabenazine autoradiography.
The monoaminergic innervation of the caudate nucleus, putamen and ventral striatum was investigated post mortem, in patients with Parkinson's and Alzheimer's disease as compared to control subjects, by autoradiographic detection of tritiated dihydrotetrabenazine (3H-TBZOH), a specific high affinity ligand of the vesicular monoamine transporter. The binding of 3H-TBZOH was specific and saturable (Kd 5.3 nM). In control striatum, the pattern of distribution of 3H-TBZOH binding was heterogeneous, with higher binding levels in the 'matrix' than in the 'striosome' compartment. Changes in ligand binding levels were observed in the pathological brains compared to controls. In Parkinson's disease (PD), characterized by a severe damage of mesostriatal dopaminergic neurons, the density of 3H-TBZOH binding was reduced. A severe decrease in 3H-TBZOH binding was observed in all parts of the striatum (caudate nucleus: -80%, putamen: -86%, ventral striatum: -94%) in PD brains. The data corroborate the deficiency in striatal dopaminergic transmission and suggest that in PD brains dopaminergic terminals have disappeared and/or no longer contain synaptic vesicles. In Alzheimer's disease (AD), 3H-TBZOH binding was significantly reduced by 57% in the ventral striatum and not in the caudate nucleus and putamen. The specific decrease of monoaminergic transporter levels in the ventral striatum confirm that this nucleus is a target area in AD.
Lehéricy
S
S
Laboratoire de Médecine Expérimentale, INSERM U 289, Hôpital de la Salpêtrière, Paris, France.
Brandel
J P
JP
Hirsch
E C
EC
Anglade
P
P
Villares
J
J
Scherman
D
D
Duyckaerts
C
C
Javoy-Agid
F
F
Agid
Y
Y
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D001345:Autoradiography; D001665:Binding Sites; D015306:Biogenic Monoamines / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000378:metabolism*; D012016:Reference Values; D013747:Tetrabenazine / Q000031:analogs & derivatives / Q000378:metabolism; D014316:Tritium
D015306:Biogenic Monoamines; D014316:Tritium; C032811:dihydrotetrabenazine; D013747:Tetrabenazine