11C-UCB-J synaptic PET and multimodal imaging in dementia with Lewy bodies
Open accessAbstract
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 11 C-UCB-J, a ligand for presynaptic vesicle protein 2A (SV2A), a vesicle membrane protein ubiquitously expressed in synapses. Methods: We performed 11 C-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 (11 C-PiB) and tau (18 F-AV-1451).11 C-UCB-J binding was quantified using non-displaceable binding potential (BP ND) determined from dynamic imaging. Changes in 11 C-UCB-J binding were correlated with MRI regional brain volume,11 C-PiB uptake and 18 F-AV-1451 binding. Results: Compared to controls, both patients had decreased 11 C-UCB-J binding, especially in parietal and occipital regions (FDR-corrected p< 0.05). There were no significant correlations across regions between 11 C-UCB-J binding and grey matter, tau (18 F-AV1451) or amyloid (11 C-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.
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Severe synaptic loss has been observed using 11C-UCBJ PET in series of cases with DLB, FTD, PD, PDD, PSP, CBD, and C9Orf72 mutation carriers.
“while severe synaptic loss has been observed using 11C -UCBJ PET in series of cases with DLB, FTD, PD, PDD, PSP, CBD and C9Orf72 mutation carriers [205–209].”
From The use of neuroimaging techniques in the early and differential diagnosis of dementia (2023) · cites this paper as [209]
The Discussion reports marked synaptic loss on 11C-UCB-J PET in two DLB cases and cites reduced binding in PD; the Introduction also reports reductions in progressive supranuclear palsy and corticobasal degeneration. The paper does not address the claimed PET findings in FTD, PDD, or C9orf72 mutation carriers, so it supports only part of the multi-condition sentence. (LLM, conf=0.86)
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- Authors
- Nicastro, N., Holland, N., Savulich, G., Carter, S. F., Mak, E., Hong, Y. T., Milicevic Sephton, S., Fryer, T. D., Aigbirhio, F. I., Rowe, J. B., & O’Brien, J. T.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Nicastro, Nicolas
- ORCID
- Venue
- European Journal of Hybrid Imaging
- Published
- 2020-12
- Volume
- 4
- Issue
- 1
- Pages
- 25-25
- ISSN
- 2510-3636 (ISSN-L)
- PMC
- PMC7752786
- OpenAlex
- W3116208050
- Cited by
- 28
- References
- 17
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 6 · 2022: 7 · 2021: 5
- FWCI
- 3.28
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- European Journal of Hybrid Imaging (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo (cc-by)
- Funders
- Wellcome Trust (103838)
- NIHR Cambridge MRC CBU
- Cambridge Center for Parkinson Plus
- Patrick Berthoud Charitable Trust
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- dementia with Lewy bodies, [11C]UCB-J, synaptic density, synaptic loss, amyloid, tau protein, [11C]PIB, 18F-AV-1451, multimodal imaging, non-displaceable binding potential, brain atrophy
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