In vivo positron emission tomographic evidence for compensatory changes in presynaptic dopaminergic nerve terminals in Parkinson's disease

TLDR

Clinical symptoms of Parkinson's disease (PD) do not manifest until dopamine neuronal loss reaches a symptomatic threshold. The study aimed to investigate compensatory mechanisms in presynaptic dopamine terminals in PD by comparing striatal PET measurements with three tracers. PET scans were performed on 35 PD patients and 16 controls using each tracer, and measurements were compared across disease stages, treatment status, and striatal subregions, with quantitative relationships between tracers analyzed. Reduced [18F]dopa uptake was less pronounced than reduced [11C]DTBZ binding, while [11C]methylphenidate binding was more reduced, indicating up‑regulation of aromatic L‑amino acid decarboxylase and down‑regulation of the plasma membrane dopamine transporter in PD striatum. Ann Neurol 2000;47:493–503.

Abstract

Clinical symptoms of Parkinson's disease (PD) do not manifest until dopamine (DA) neuronal loss reaches a symptomatic threshold. To explore the mechanisms of functional compensation that occur in presynaptic DA nerve terminals in PD, we compared striatal positron emission tomographic (PET) measurements by using [11C]dihydrotetrabenazine ([11C]DTBZ; labeling the vesicular monoamine transporter type 2), [11C]methylphenidate (labeling the plasma membrane DA transporter), and [18F]dopa (reflecting synthesis and storage of DA). Three consecutive PET scans were performed in three-dimensional mode by using each tracer on 35 patients and 16 age-matched, normal controls. PET measurements by the three tracers were compared between subgroups of earlier and later stages of PD, between drug-naive and drug-treated subgroups of PD, and between subregions of the parkinsonian striatum. The quantitative relationships of [18F]dopa and [11C]DTBZ, and of [11C]methylphenidate and [11C]DTBZ, were compared between the PD and the normal control subjects. We found that [18F]dopa Ki was reduced less than the binding potential (Bmax/Kd) for [11C]DTBZ in the parkinsonian striatum, whereas the [11C]methylphenidate binding potential was reduced more than [11C]DTBZ binding potential. These observations suggest that the activity of aromatic L-amino acid decarboxylase is up-regulated, whereas the plasma membrane DA transporter is down-regulated in the striatum of patients with PD. Ann Neurol 2000;47:493–503.