Synaptic density in carriers of C9orf72 mutations: a [11C]UCB‐J PET study
Open accessAbstract
Synaptic loss is an early and clinically relevant feature of many neurodegenerative diseases. Here we assess three adults at risk of frontotemporal dementia from C9orf72 mutation, using [11 C]UCB‐J PET to quantify synaptic density in comparison with 19 healthy controls and one symptomatic patient with behavioural variant frontotemporal dementia. The three pre‐symptomatic C9orf72 carriers showed reduced synaptic density in the thalamus compared to controls, and there was an additional extensive synaptic loss in frontotemporal regions of the symptomatic patient. [11 C]UCB‐J PET may facilitate early, pre‐symptomatic assessment, monitoring of disease progression and evaluation of new preventive treatment strategies for frontotemporal dementia.
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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 [208]
The Results report reduced thalamic [11C]UCB-J binding in each of three presymptomatic C9orf72 mutation carriers. They describe widespread severe synaptic loss in the symptomatic FTD patient, but do not characterize the loss in all three carriers as severe. This paper supports the C9orf72 portion of the grouped citation, with that severity qualification. (LLM, conf=0.84)
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- Authors
- Malpetti, M., Holland, N., Jones, P. S., Ye, R., Cope, T. E., Fryer, T. D., Hong, Y. T., Savulich, G., Rittman, T., Passamonti, L., Mak, E., Aigbirhio, F. I., O’Brien, J. T., & Rowe, J. B.
- Affiliations
- University of Cambridge (GB)
- MRC Cognition and Brain Sciences Unit (GB)
- Cambridge University Hospitals NHS Foundation Trust Cambridge UK
- Corresponding author
- Malpetti, Maura
- ORCID
- Venue
- Annals of Clinical and Translational Neurology
- Publisher
- Wiley
- Published
- 2021-06-16
- Volume
- 8
- Issue
- 7
- Pages
- 1515-1523
- ISSN
- 2328-9503 (ISSN-L)
- PMC
- PMC8283163
- OpenAlex
- W3166602195
- Cited by
- 44
- References
- 28
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 12 · 2023: 11 · 2022: 12 · 2021: 1
- FWCI
- 4.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Annals of Clinical and Translational Neurology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Wellcome Trust (220258)
- NIHR Cambridge Biomedical Research Centre (BRC‐1215‐20014)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- C9orf72 mutation, frontotemporal dementia, synaptic density, behavioral variant frontotemporal dementia, neurodegeneration, early disease detection
- MeSH terms
- C9orf72 Protein, Carbon Radioisotopes, Female, Heterozygote, Humans, Male, Middle Aged, Mutation, Pyridines, Pyrrolidinones, Synapses, Positron-Emission Tomography, Frontotemporal Dementia
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