11C-UCB-J synaptic PET and multimodal imaging in dementia with Lewy bodies

ObjectiveDementia with Lewy bodies (DLB) is a common cause of dementia, but atrophy is mild compared to Alzheimer's disease. We propose that DLB is associated instead with severe synaptic loss, and we test this hypothesis in vivo using positron emission tomography (PET) imaging of C-11-UCB-J, a ligand for presynaptic vesicle protein 2A (SV2A), a vesicle membrane protein ubiquitously expressed in synapses.MethodsWe performed C-11-UCB-J PET in two DLB patients (an amyloid-negative male and an amyloid-positive female in their 70s) and 10 similarly aged healthy controls. The DLB subjects also underwent PET imaging of amyloid (C-11-PiB) and tau (F-18-AV-1451). C-11-UCB-J binding was quantified using non-displaceable binding potential (BPND) determined from dynamic imaging. Changes in C-11-UCB-J binding were correlated with MRI regional brain volume, C-11-PiB uptake and F-18-AV-1451 binding.ResultsCompared to controls, both patients had decreased C-11-UCB-J binding, especially in parietal and occipital regions (FDR-corrected p < 0.05). There were no significant correlations across regions between C-11-UCB-J binding and grey matter, tau (F-18-AV1451) or amyloid (C-11-PiB) in either patient.ConclusionsQuantitative imaging of in vivo synaptic density in DLB is a promising approach to understanding the mechanisms of DLB, over and above changes in grey matter volume and concurrent amyloid/tau deposition.