Synaptic Loss in Primary Tauopathies Revealed by [11 C]UCB-J Positron Emission Tomography.
Authors
Savulich, George
Wiggins, Julie K
Hong, Young
Fryer, Timothy
Boros, Istvan
Publication Date
2020-10Journal Title
Mov Disord
ISSN
0885-3185
Publisher
Wiley
Volume
35
Issue
10
Pages
1834-1842
Language
eng
Type
Article
This Version
VoR
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Holland, N., Jones, S., Savulich, G., Wiggins, J. K., Hong, Y., Fryer, T., Manavaki, R., et al. (2020). Synaptic Loss in Primary Tauopathies Revealed by [11 C]UCB-J Positron Emission Tomography.. Mov Disord, 35 (10), 1834-1842. https://doi.org/10.1002/mds.28188
Abstract
BACKGROUND: Synaptic loss is a prominent and early feature of many neurodegenerative diseases. OBJECTIVES: We tested the hypothesis that synaptic density is reduced in the primary tauopathies of progressive supranuclear palsy (PSP) (Richardson's syndrome) and amyloid-negative corticobasal syndrome (CBS). METHODS: Forty-four participants (15 CBS, 14 PSP, and 15 age-/sex-/education-matched controls) underwent PET with the radioligand [11 C]UCB-J, which binds to synaptic vesicle glycoprotein 2A, a marker of synaptic density; participants also had 3 Tesla MRI and clinical and neuropsychological assessment. RESULTS: Nine CBS patients had negative amyloid biomarkers determined by [11 C]PiB PET and hence were deemed likely to have corticobasal degeneration (CBD). Patients with PSP-Richardson's syndrome and amyloid-negative CBS were impaired in executive, memory, and visuospatial tasks. [11 C]UCB-J binding was reduced across frontal, temporal, parietal, and occipital lobes, cingulate, hippocampus, insula, amygdala, and subcortical structures in both PSP and CBD patients compared to controls (P < 0.01), with median reductions up to 50%, consistent with postmortem data. Reductions of 20% to 30% were widespread even in areas of the brain with minimal atrophy. There was a negative correlation between global [11 C]UCB-J binding and the PSP and CBD rating scales (R = -0.61, P < 0.002; R = -0.72, P < 0.001, respectively) and a positive correlation with the revised Addenbrooke's Cognitive Examination (R = 0.52; P = 0.01). CONCLUSIONS: We confirm severe synaptic loss in PSP and CBD in proportion to disease severity, providing critical insight into the pathophysiology of primary degenerative tauopathies. [11 C]UCB-J may facilitate treatment strategies for disease-modification, synaptic maintenance, or restoration. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Keywords
Humans, Supranuclear Palsy, Progressive, Alzheimer Disease, Tauopathies, Atrophy, Positron-Emission Tomography
Sponsorship
Patrick Berthoud Charitable Trust (via Charities Aid Foundation) (Unknown)
Wellcome Trust (103838/Z/14/Z)
MRC (unknown)
Cambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
Medical Research Council (MR/M024873/1)
Medical Research Council (MC_U105597119)
Medical Research Council (MR/M009041/1)
Medical Research Council (MC_UU_00005/12)
Embargo Lift Date
2100-01-01
Identifiers
External DOI: https://doi.org/10.1002/mds.28188
This record's URL: https://www.repository.cam.ac.uk/handle/1810/306715
Rights
Attribution 4.0 International (CC BY)
Licence URL: http://creativecommons.org/licenses/by/4.0/
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