Toft, Anders;
Sjödin, Simon;
Simonsen, Anja Hviid;
Ejlerskov, Patrick;
Roos, Peter;
Musaeus, Christian Sandøe;
Henriksen, Emil Elbæk;
... Nielsen, Jørgen Erik; + view all
(2023)
Endo-lysosomal protein concentrations in CSF from patients with frontotemporal dementia caused by CHMP2B mutation.
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
, 15
(1)
, Article e12402. 10.1002/dad2.12402.
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Abstract
INTRODUCTION: Increasing evidence implicates proteostatic dysfunction as an early event in the development of frontotemporal dementia (FTD). This study aimed to explore potential cerebrospinal fluid (CSF) biomarkers associated with the proteolytic systems in genetic FTD caused by CHMP2B mutation. METHODS: Combining solid-phase extraction and parallel reaction monitoring mass spectrometry, a panel of 47 peptides derived from 20 proteins was analyzed in CSF from 31 members of the Danish CHMP2B-FTD family. RESULTS: Compared with family controls, mutation carriers had significantly higher levels of complement C9, lysozyme and transcobalamin II, and lower levels of ubiquitin, cathepsin B, and amyloid precursor protein. DISCUSSION: Lower CSF ubiquitin concentrations in CHMP2B mutation carriers indicate that ubiquitin levels relate to the specific disease pathology, rather than all-cause neurodegeneration. Increased lysozyme and complement proteins may indicate innate immune activation. Altered levels of amyloid precursor protein and cathepsins have previously been associated with impaired lysosomal proteolysis in FTD. HIGHLIGHTS: CSF markers of proteostasis were explored in CHMP2B-mediated frontotemporal dementia (FTD).31 members of the Danish CHMP2B-FTD family were included.We used solid-phase extraction and parallel reaction monitoring mass spectrometry.Six protein levels were significantly altered in CHMP2B-FTD compared with controls.Lower CSF ubiquitin levels in patients suggest association with disease mechanisms.
| Type: | Article |
|---|---|
| Title: | Endo-lysosomal protein concentrations in CSF from patients with frontotemporal dementia caused by CHMP2B mutation |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/dad2.12402 |
| Publisher version: | https://doi.org/10.1002/dad2.12402 |
| Language: | English |
| Additional information: | © 2023 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
| Keywords: | amyloid precursor protein, biomarkers, cathepsin B, cerebrospinal fluid, complement C9, frontotemporal dementia, lysozyme, proteomics, transcobalamin II, ubiquitin |
| 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.ucl.ac.uk/id/eprint/10168909 |
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