Zetterberg, Henrik;
Teunissen, Charlotte;
van Swieten, John;
Kuhle, Jens;
Boxer, Adam;
Rohrer, Jonathan D;
Mitic, Laura;
... Tatton, Nadine; + view all
(2023)
The role of neurofilament light in genetic frontotemporal lobar degeneration.
Brain Communications
, 5
(1)
, Article fcac310. 10.1093/braincomms/fcac310.
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Abstract
Genetic frontotemporal lobar degeneration caused by autosomal dominant gene mutations provides an opportunity for targeted drug development in a highly complex and clinically heterogeneous dementia. These neurodegenerative disorders can affect adults in their middle years, progress quickly relative to other dementias, are uniformly fatal, and have no approved disease modifying treatments. Frontotemporal dementia, caused by mutations in the GRN gene which encodes the protein progranulin, is an active area of interventional drug trials that are testing multiple strategies to restore progranulin protein deficiency. These and other trials are also examining neurofilament light as a potential biomarker of disease activity and disease progression, and as a therapeutic endpoint based on the assumption that cerebrospinal fluid and blood neurofilament light levels are a surrogate for neuroaxonal damage. Reports from genetic frontotemporal dementia longitudinal studies indicate that elevated concentrations of blood neurofilament light reflect disease severity and are associated with faster brain atrophy. To better inform patient stratification and treatment response in current and upcoming clinical trials, a more nuanced interpretation of neurofilament light as a biomarker of neurodegeneration is now required, one that takes into account its relationship to other pathophysiological and topographic biomarkers of disease progression from early presymptomatic to later clinically symptomatic stages.
| Type: | Article |
|---|---|
| Title: | The role of neurofilament light in genetic frontotemporal lobar degeneration |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/braincomms/fcac310 |
| Publisher version: | https://doi.org/10.1093/braincomms/fcac310 |
| Language: | English |
| Additional information: | Copyright © The Author(s) 2022. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | frontotemporal lobar degeneration, neurofilament light, trial stratification, disease progression, frontotemporal dementia |
| 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 > Neurodegenerative Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10161682 |
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