Striatal dopamine deficiency in Parkinson's disease: role of aging

Abstract

The striatal dopaminergic innervation was investigated postmortem in 49 control and 57 parkinsonian brains by assessing the binding of tritiated alpha-dihydrotetrabenazine ([3H]TBZOH), a specific ligand of the vesicular monoamine transporter. The density of [3H]TBZOH binding sites in the caudate nucleus of control subjects decreased significantly with age, suggesting an age-dependent reduction in striatal dopamine innervation. In contrast, an increase with the age at time of death was observed in patients with Parkinson's disease, although the density of [3H]TBZOH binding sites was subnormal. Mean values represented 26.5% and 12.7% of control values in the caudate nucleus and in the putamen, respectively. The binding of [3H]TBZOH in the caudate nucleus decreased exponentially with the duration of Parkinson's disease. The rate of [3H]TBZOH binding decrease, an index of the rate of striatal dopaminergic denervation, was about twice as high in parkinsonian patients as in controls and was not related to the age at onset of the disease. The data suggest that (1) parkinsonian symptoms appear above a threshold degeneration state corresponding to 50% of the normal innervation at the age of 60, and (2) aging does not play a major role in the process of nigrostriatal neuron degeneration in Parkinson's disease.