Weston, PSJ;
Poole, T;
O'Connor, A;
Heslegrave, A;
Ryan, NS;
Liang, Y;
Druyeh, R;
... Fox, NC; + view all
(2019)
Longitudinal measurement of serum neurofilament light in presymptomatic familial Alzheimer's disease.
Alzheimer's Research & Therapy
, 11
, Article 19. 10.1186/s13195-019-0472-5.
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Abstract
BACKGROUND: To investigate how serum neurofilament light (NfL) concentration changes through the course of disease in familial Alzheimer's disease (FAD) and to assess when NfL concentration first increases. METHODS: NfL was measured using an ultrasensitive immunoassay in 117 serum samples from 61 individuals from families with PSEN1 or APP mutations in a longitudinal study (mean ± SD = 1.9 ± 1.1 visits/patient; inter-visit interval = 1.8 ± 1.1 years). The relationship between NfL concentration and estimated years to/from symptom onset (EYO) was modelled using linear regression, including all time points and robust standard errors to allow for repeated measurements, adjusting for age at visit and sex. Also, for the 27 participants who became symptomatic (during or before the study), NfL concentration was also modelled against known actual years to/from onset (AYO). RESULTS: There were 15 non-carriers and 46 mutation carriers (21 symptomatic; 25 presymptomatic). NfL concentration was increased (p = 0.045) in mutation carriers compared with non-carriers 15 years prior to expected symptom onset, increasing progressively thereafter. There was a significant inter- and intra-individual variability in the longitudinal pattern of change. Modelling NfL for the 27 mutation carriers with known AYO also showed a progressive increase over time. CONCLUSIONS: There is evidence that serum NfL is increased more than a decade before the onset of clinical symptoms in FAD and rises thereafter. While there is variability in change over time, both within and between individuals, and more work is needed to understand the sources of this variability, serum NfL remains a promising, accessible biomarker of early neurodegeneration in presymptomatic Alzheimer's disease.
| Type: | Article |
|---|---|
| Title: | Longitudinal measurement of serum neurofilament light in presymptomatic familial Alzheimer's disease |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1186/s13195-019-0472-5 |
| Publisher version: | https://doi.org/10.1186/s13195-019-0472-5 |
| Language: | English |
| Additional information: | © The Author(s) 2019. Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
| Keywords: | Search terms, [111] blood, [111] longitudinal, [111] neurofilament light, [26] Alzheimer’s disease, [91] autosomal dominant |
| 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 Institute of Prion Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Institute of Prion Diseases > MRC Prion Unit at UCL 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/10068850 |
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