Johansson, Kalle;
Wasling, Pontus;
Novakova, Lenka;
Sjödin, Simon;
Brinkmalm, Ann;
Brinkmalm, Gunnar;
Blennow, Kaj;
... Axelsson, Markus; + view all
(2022)
Cerebrospinal fluid amyloid precursor protein as a potential biomarker of fatigue in multiple sclerosis: A pilot study.
Multiple Sclerosis and Related Disorders
, 63
, Article 103846. 10.1016/j.msard.2022.103846.
(In press).
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Abstract
BACKGROUND: Fatigue is the major cause of disability in MS. Fatigue has been suggested to be primary, part of the neurological disease; it can also be secondary to other diseases outside the CNS or exist as a separate comorbidity. The only forms of measurement currently available are through subjective standardized questionnaires, which are not able to identify primary MS-related fatigue. Therefore, there is a need for objective biomarkers of fatigue in MS. This study explored the viability of 17 possible biomarkers of primary fatigue in MS. Our chosen biomarker panel represents the function and health of different parts of the CNS. METHODS: We evaluated 31 MS patients and 17 healthy controls using the Fatigue Severity Scale (FSS) and Insomnia Severity Index (ISI). We assessed clinical parameters and collected CSF from all participants to analyze 17 biomarkers, some of which in multiple targeted sequences, reflecting structural and functional changes in the brain. Based on FSS scores, MS was divided into MS-Fatigue (MS-F, FSS ≥ 4) and MS-NoFatigue (MS-NoF, FSS < 4). RESULTS: MS-F had significantly lower levels of amyloid precursor protein (APP) peptides than MS-NoF (p = 0.005, p = 0.011). The only biomarker correlating with FSS in any group was APP in MS (r = -0.47, -0.52; p = 0.007, 0.002). APP did not correlate with any clinical parameter in MS but correlated with multiple markers. In MS, FSS correlated with the ISI and months since diagnosis. CONCLUSION: Although the mechanisms remain unknown, altered APP metabolism in MS seems to be associated with fatigue. APP should be evaluated as a biomarker of the role of structural MS pathology in the development of fatigue in individual MS patients.
| Type: | Article |
|---|---|
| Title: | Cerebrospinal fluid amyloid precursor protein as a potential biomarker of fatigue in multiple sclerosis: A pilot study |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.msard.2022.103846 |
| Publisher version: | https://doi.org/10.1016/j.msard.2022.103846 |
| Language: | English |
| Additional information: | © 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Amyloid precursor protein, Biomarker, Fatigue, ISI, Insomnia, MS, Neuropentraxin-1, FSS |
| UCL classification: | 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 > Neurodegenerative Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10148655 |
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