PET imaging of amyloid with Florbetapir F 18 and PET imaging of dopamine degeneration with 18F-AV-133 (florbenazine) in patients with Alzheimer’s disease and Lewy body disorders

Abstract

BackgroundBiomarkers based on the underlying pathology of Alzheimer’s disease (AD) and Dementia with Lewy Bodies (DLB) have the potential to improve diagnosis and understanding of the substrate for cognitive impairment in these disorders. The objective of this study was to compare the patterns of amyloid and dopamine PET imaging in patients with AD, DLB and Parkinson’s disease (PD) using the amyloid imaging agent florbetapir F 18 and 18F-AV-133 (florbenazine), a marker for vesicular monamine type 2 transporters (VMAT2).MethodsPatients with DLB and AD, Parkinson’s disease (PD) and healthy controls (HC) were recruited for this study. On separate days, subjects received intravenous injections of florbetapir, and florbenazine. Amyloid burden and VMAT2 density were assessed quantitatively and by binary clinical interpretation. Imaging results for both tracers were compared across the four individual diagnostic groups and for combined groups based on underlying pathology (AD/DLB vs. PD/HC for amyloid burden and PD/DLB vs. AD/HC for VMAT binding) and correlated with measures of cognition and parkinsonism.Results11 DLB, 10 AD, 5 PD, and 5 controls participated in the study. Amyloid binding was significantly higher in the combined AD/DLB patient group (n = 21) compared to the PD/HC groups (n = 10, mean SUVr: 1.42 vs. 1.07; p = 0.0006). VMAT2 density was significantly lower in the PD/DLB group (n = 16) compared to the AD/ HC group (n = 15; 1.83 vs. 2.97; p < 0.0001). Within the DLB group, there was a significant correlation between cognitive performance and striatal florbenazine binding (r = 0.73; p = 0.011).ConclusionsThe results of this study show significant differences in both florbetapir and florbenazine imaging that are consistent with expected pathology. In addition, VMAT density correlated significantly with cognitive impairment in DLB patients (ClinicalTrials.gov identifier: NCT00857506, registered March 5, 2009).

The Parkinson's progression markers initiative (PPMI) – establishing a PD biomarker cohort

“…All subjects had dopaminergic imaging with either 123I Ioflupane targeting the dopamine transporter (DAT‐SPECT) or 18F AV133 (Australian site only) targeting the vesicular monoamine transporter (VMAT‐PET) at screening according to the imaging technical operations manual (www.ppmi‐info.org) 20, 21, 22, 23, 24. To ensure technical standardization across multiple sites and cameras employed in this study, a central core imaging laboratory developed a program for technical qualification, quality assurance, and ongoing camera quality control.…”

Imaging in Parkinson's Disease

“…Amyloid burden in PDD patients is heterogeneous with cases of PDD, where amyloid deposition overlaps with the levels observed in healthy subjects and in PD patients (Edison et al, 2013(Edison et al, , 2008Foster et al, 2010;Gomperts et al, 2012Gomperts et al, , 2008Jokinen et al, 2010;Maetzler et al, 2009Maetzler et al, , 2008 and other cases of PDD showing elevated cortical amyloid deposition in the Alzheimer's disease (AD) range (Edison et al, 2013(Edison et al, , 2008Foster et al, 2010;Gomperts et al, 2012;Jokinen et al, 2010;Maetzler et al, 2009Maetzler et al, , 2008Shimada et al, 2013). In contrast, amyloid burden is usually elevated in DLB patients compared to healthy subjects and PD patients and the incidence ranges between 33% and 100% (Burke et al, 2011;Claassen, Lowe, Peller, Petersen, & Josephs, 2011;Edison et al, 2008;Foster et al, 2010;Gomperts et al, 2012Gomperts et al, , 2008Graff-Radford et al, 2012;Kantarci et al, 2012;Maetzler et al, 2009Maetzler et al, , 2008Rowe et al, 2007;Siderowf et al, 2014;Villemagne et al, 2011).…”

“…However, extracellular Aβ-amyloid plaques and intracellular tau neurofibrillary tangle are also observed at autopsy in PD, PDD, and DLB patients (Horvath, Herrmann, Burkhard, Bouras, & K€ ovari, 2013;Jellinger & Attems, 2008;Jellinger, Seppi, Wenning, & Poewe, 2002 of amyloid deposition in PD, PDD, and DLB. Overall these studies found that amyloid deposition tends to be modest in PD with normal cognition occurring in about 0%-13% of PD patients (Edison et al, 2013(Edison et al, , 2008Foster et al, 2010;Gomperts et al, 2012Gomperts et al, , 2008Johansson et al, 2008;Jokinen et al, 2010;Maetzler et al, 2009;Siderowf et al, 2014;Villemagne et al, 2011). Amyloid burden is generally low in PD subjects with mild cognitive impairment (MCI), and does not distinguish cognitively normal PD patients from PD-MCI (Foster et al, 2010;Gomperts et al, 2012Gomperts et al, , 2013Petrou et al, 2012).…”

Associations between 18F-AV133 Cerebral VMAT2 Binding and Plasma LDL and HDL Levels in Parkinson’s Disease

“…Since cholesterol metabolism is associated with Parkinson's disease pathogenesis and progression [13,18], and VMAT2 imaging has proven to be an objective marker for monoaminergic neuron synaptic integrity [6,9,19], it is plausible to predict a similar correlation between the monoamine neuronal integrity marker and serum lipid levels. To evaluate this hypothesis, we investigated the associations between plasma lipid indicators (including total cholesterol, high-density lipoprotein (HDL), low density lipoprotein (LDL), and triglycerides) and cerebral VMAT2 densities assessed by 18 F-AV133 PET in PD patients.…”