Whiteside, DJ;
Holland, N;
Tsvetanov, KA;
Mak, E;
Malpetti, M;
Savulich, G;
Jones, PS;
... Rowe, JB; + view all
(2023)
Synaptic density affects clinical severity via network dysfunction in syndromes associated with frontotemporal lobar degeneration.
Nature Communications
, 14
, Article 8458. 10.1038/s41467-023-44307-7.
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Abstract
There is extensive synaptic loss from frontotemporal lobar degeneration, in preclinical models and human in vivo and post mortem studies. Understanding the consequences of synaptic loss for network function is important to support translational models and guide future therapeutic strategies. To examine this relationship, we recruited 55 participants with syndromes associated with frontotemporal lobar degeneration and 24 healthy controls. We measured synaptic density with positron emission tomography using the radioligand [11C]UCB-J, which binds to the presynaptic vesicle glycoprotein SV2A, neurite dispersion with diffusion magnetic resonance imaging, and network function with task-free magnetic resonance imaging functional connectivity. Synaptic density and neurite dispersion in patients was associated with reduced connectivity beyond atrophy. Functional connectivity moderated the relationship between synaptic density and clinical severity. Our findings confirm the importance of synaptic loss in frontotemporal lobar degeneration syndromes, and the resulting effect on behaviour as a function of abnormal connectivity.
| Type: | Article |
|---|---|
| Title: | Synaptic density affects clinical severity via network dysfunction in syndromes associated with frontotemporal lobar degeneration |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41467-023-44307-7 |
| Publisher version: | http://dx.doi.org/10.1038/s41467-023-44307-7 |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10184825 |
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