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

Published version
Peer-reviewed

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Authors

Holland, Negin 
Savulich, George 
Carter, Stephen F. 
Mak, Elijah 

Abstract

Abstract: Objective: Dementia 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 11C-UCB-J, a ligand for presynaptic vesicle protein 2A (SV2A), a vesicle membrane protein ubiquitously expressed in synapses. Methods: We performed 11C-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 (11C-PiB) and tau (18F-AV-1451). 11C-UCB-J binding was quantified using non-displaceable binding potential (BPND) determined from dynamic imaging. Changes in 11C-UCB-J binding were correlated with MRI regional brain volume, 11C-PiB uptake and 18F-AV-1451 binding. Results: Compared to controls, both patients had decreased 11C-UCB-J binding, especially in parietal and occipital regions (FDR-corrected p < 0.05). There were no significant correlations across regions between 11C-UCB-J binding and grey matter, tau (18F-AV1451) or amyloid (11C-PiB) in either patient. Conclusions: Quantitative 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.

Description

Funder: NIHR Cambridge MRC CBU


Funder: Cambridge Center for Parkinson Plus


Funder: Patrick Berthoud Charitable Trust; doi: http://dx.doi.org/10.13039/501100004218

Keywords

Case Report, Synaptic imaging, Dementia, Lewy bodies, Amyloid, Tau, Brain atrophy

Journal Title

European Journal of Hybrid Imaging

Conference Name

Journal ISSN

2510-3636

Volume Title

4

Publisher

Springer International Publishing
Sponsorship
Wellcome Trust (103838)