18F-AV-1451 in Parkinson's Disease with and without dementia and in Dementia with Lewy Bodies

Abstract

Mixed pathologies of α-synuclein, β-amyloid and tau are relatively common in Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). We therefore wanted to study the retention patterns of ¹⁸F-AV-1451 in PD, PD-dementia (PDD), and DLB. To do this 44 healthy controls, 11 non-demented patients with PD, 18 patients with PDD, and six patients with DLB underwent MRI and ¹⁸F-AV-1451 PET scanning and cognitive testing. We found that parietal ¹⁸F-AV-1451 retention was increased in patients with DLB compared to controls and PD patients, while ¹⁸F-AV-1451 uptake was reduced in the substantia nigra in PDD. Increased parietal ¹⁸F-AV-1451 PET uptake was associated with impaired performance on verbal fluency tests, and the decreased uptake in the substantia nigra correlated with worse motor function. We found no effect of the monoamine oxidase B inhibitor rasagiline on ¹⁸F-AV-1451 binding. In conclusion DLB patients have increased parietal ¹⁸F-AV-1451 uptake. Increased parietal tau is associated with executive impairment in patients with synucleinopathies, while decreased uptake in the substantia nigra is associated with parkinsonism. Further, our data indicate that ¹⁸F-AV-1451 does not significantly bind to MAO-B in vivo.

Figure 1

¹⁸F-AV-1451 retention in cortical and subcortical regions. ¹⁸F-AV-1451 SUVRs in the frontal cortex (A), medial parietal cortex (B), lateral parietal cortex (C) and occipital cortex (D). Amyloid positive subjects are represented by red shapes and amyloid negative subjects by black shapes. Correlations of medial (E) and lateral (F) parietal cortex SUVRs to Letter S-fluency scores. PD = blue squares; PDD = black triangles; DLB = green inverted triangles. (G) The effect of MAO-B inhibition on SUVRs in the globus pallidus. (H) ¹⁸F-AV-1451 SUVRs in the substantia nigra. (I) Correlation of ¹⁸F-AV-1451 SUVRs in the substantia nigra and the Unified Parkinson’s Disease Rating Scale (UPDRS) motor score. (J) Lateral and medial view of average SUVR images of the diagnostic groups studied. The rightmost column represents an average SUVR image of typical AD-cases (n = 41) that have been included merely for visual comparison. White color in the AD images represents saturation of the SUVR-scale (i.e. SUVR > 2). Ctrl - controls; DLB - Dementia with Lewy Bodies; Inh - inhibitor; MAO-B - monoamine oxidase B; PD - Parkinson’s Disease; PDD - Parkinson’s Disease with dementia; V_d – Volume of distribution. *p < 0.05, **p < 0.01, ***p < 0.001.