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Longitudinal measur...
Longitudinal measurement of serum neurofilament light in presymptomatic familial Alzheimer's disease
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Weston, P. S. J. (author)
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Poole, T. (author)
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O'Connor, A. (author)
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Heslegrave, A. (author)
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Ryan, N. S. (author)
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Liang, Y. Y. (author)
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Druyeh, R. (author)
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Mead, S. (author)
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- Blennow, Kaj, 1958 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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Schott, J. M. (author)
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Frost, C. (author)
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- Zetterberg, Henrik, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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Fox, N. C. (author)
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(creator_code:org_t)
- 2019-02-20
- 2019
- English.
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In: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 11:1
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https://alzres.biome...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
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- BackgroundTo 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.MethodsNfL was measured using an ultrasensitive immunoassay in 117 serum samples from 61 individuals from families with PSEN1 or APP mutations in a longitudinal study (meanSD=1.91.1 visits/patient; inter-visit interval=1.8 +/- 1.1years). 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 15years 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 increaseover 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Search terms
- [26] Alzheimer's disease
- [91] autosomal dominant
- [111] neurofilament light
- [111] blood
- [111] longitudinal
- neurodegeneration
- Neurosciences & Neurology
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Weston, P. S. J.
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Poole, T.
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O'Connor, A.
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Heslegrave, A.
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Ryan, N. S.
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Liang, Y. Y.
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show more...
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Druyeh, R.
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Mead, S.
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Blennow, Kaj, 19 ...
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Schott, J. M.
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Frost, C.
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Zetterberg, Henr ...
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Fox, N. C.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Alzheimers Resea ...
- By the university
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University of Gothenburg