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Cited by 93Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsParkinson's Disease Mechanisms and Treatments

Synaptic Loss in Primary Tauopathies Revealed by [ 11 C ] UCB‐J Positron Emission Tomography

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Holland, Negin, Jones, P. Simon, Savulich, George, Wiggins, Julie K., Hong, Young T., Fryer, Tim D., Manavaki, Roido, Sephton, Selena Milicevic +7 more·2020·Movement Disorders
DOI 10.1002/mds.28188PMC PMC7611123

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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.

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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 [207]

    The Discussion reports severe, extensive synaptic loss measured with [11C]UCB-J PET in PSP and amyloid-negative corticobasal syndrome, which the authors classify as CBD. The Methods and Results describe PSP and CBD patient groups, but do not establish the claim for DLB, FTD, PD, PDD, or C9Orf72 mutation carriers. (LLM, conf=0.88)

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Authors
Holland, N., Jones, P. S., Savulich, G., Wiggins, J. K., Hong, Y. T., Fryer, T. D., Manavaki, R., Sephton, S. M., Boros, I., Malpetti, M., Hezemans, F. H., Aigbirhio, F. I., Coles, J. P., O’Brien, J., & Rowe, J. B.
Affiliations
  • University of Cambridge (GB)
  • Department of Clinical Neurosciences University of Cambridge Cambridge United Kingdom
  • MRC Cognition and Brain Sciences Unit (GB)
  • Department of Psychiatry University of Cambridge Cambridge United Kingdom
Corresponding author
Holland, Negin
ORCID
Venue
Movement Disorders
Publisher
Wiley
Published
2020-07-11
Volume
35
Issue
10
Pages
1834-1842
ISSN
  • 0885-3185 (ISSN-L)
  • 1531-8257
DOI
10.1002/mds.28188
PMC
PMC7611123
OpenAlex
W3040935827
Cited by
93
References
65
Citations by year
2026: 7 · 2025: 10 · 2024: 17 · 2023: 16 · 2022: 23 · 2021: 16 · 2020: 4
FWCI
10.76
Type
journal article
Language
en
Open access
Licence
Locations
  • Movement Disorders (publishedVersion, cc-by)
  • medRxiv (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Apollo (cc-by)
Funders
  • National Institute for Health Research (146281)
  • Medical Research Council (SUAG/004, RG91365)
  • Patrick Berthoud Charitable Trust (RG99368)
  • Wellcome Trust (103838)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
Keywords
synaptic loss, primary tauopathies, progressive supranuclear palsy, corticobasal degeneration, corticobasal syndrome, SV2A, synaptic density, cognitive impairment, disease severity, neurodegeneration
MeSH terms
Alzheimer Disease, Atrophy, Humans, Supranuclear Palsy, Progressive, Tauopathies, Positron-Emission Tomography

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