Validity of a Novel Non-Motor Symptom Scale and [C11]-DTBZ Pet-based Measures as Tools for Tracking Disease Severity in MPTP Primates

Parkinson disease (PD) is a progressive neurodegenerative disorder, characterized by marked dopaminergic loss within the midbrain and presence of Lewy bodies post-mortem. It is important to determine a way to quantify disease progression through both clinical ratings and measures of dopamine function within the brain. Using the MPTP model in the non-human primate, [C11]-DTBZ PET-based measures of binding potential in the nucleus accumbens, were used to assess disease progression in living primates. DTBZ binds to VMAT-2, a presynaptic vesicular transporter in dopamine neurons, which could be a potential biomarker of disease progression. This measure was compared to a novel non-motor scale (NMS) of manifestations that assesses apathy and anxiety rather than the more traditional motor manifestions. To understand the ability of the measures to characterize PD progression, variable doses of MPTP were given to primates, and the measures were compared to each other and post-mortem cell counts of dopamine neurons in the ventral tegmental area (VTA), the part of the midbrain that connects with limbic areas important for emotion processing. We found that the NMS was reproducible between intra-rater ratings for apathy and anxiety (κ=0.68, 0.53 respectively), and that ratings following MPTP were significantly higher based on a paired t-test (p\u3c.05). We found apathy ratings had a strong correlation with DTBZ binding potential in the NAcc (r=-0.76, p\u3c.05). Binding potential also had a strong correlation with cell counts in the VTA (r=0.79, p\u3c.05). Cell counts, binding potential, and apathy ratings all significantly correlated with MPTP dosage (r=-0.63, -0.90, 0.92; p\u3c.05). These data suggest that using the NMS and DTBZ PET measures could potentially be used to better assess a patient’s disease progression, particularly of these non-motor manifestations