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Evaluation of plasm...
Evaluation of plasma tau and neurofilament light chain biomarkers in a 12-year clinical cohort of human prion diseases.
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Thompson, Andrew G B (författare)
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Anastasiadis, Prodromos (författare)
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Druyeh, Ronald (författare)
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visa fler...
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Whitworth, Ines (författare)
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Nayak, Annapurna (författare)
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Nihat, Akin (författare)
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Mok, Tze How (författare)
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Rudge, Peter (författare)
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Wadsworth, Jonathan D F (författare)
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Rohrer, Jonathan (författare)
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Schott, Jonathan M (författare)
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Heslegrave, Amanda (författare)
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- Zetterberg, Henrik, 1973 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Collinge, John (författare)
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Jackson, Graham S (författare)
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Mead, Simon (författare)
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(creator_code:org_t)
- 2021-03-05
- 2021
- Engelska.
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Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 26, s. 5955-5966
- Relaterad länk:
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https://www.nature.c...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Prion diseases are fatal neurodegenerative conditions with highly accurate CSF and imaging diagnostic tests, but major unmet needs for blood biomarkers. Using ultrasensitive immuno-assays, we measured tau and neurofilament light chain (NfL) protein concentrations in 709 plasma samples taken from 377 individuals with prion disease during a 12year prospective clinical study, alongside healthy and neurological control groups. This provides an unprecedented opportunity to evaluate their potential as biomarkers. Plasma tau and NfL were increased across all prion disease types. For distinguishing sCJD from control groups including clinically-relevant "CJD mimics", both show considerable diagnostic value. In sCJD, NfL was substantially elevated in every sample tested, including during early disease with minimal functional impairment and in all follow-up samples. Plasma tau was independently associated with rate of clinical progression in sCJD, while plasma NfL showed independent association with severity of functional impairment. In asymptomatic PRNP mutation carriers, plasma NfL was higher on average in samples taken within 2years of symptom onset than in samples taken earlier. We present biomarker trajectories for nine mutation carriers healthy at enrolment who developed symptoms during follow-up. NfL started to rise as early as 2years before onset in those with mutations typically associated with more slowly progressive clinical disease. This shows potential for plasma NfL as a "proximity marker", but further work is needed to establish predictive value on an individual basis, and how this varies across different PRNP mutations. We conclude that plasma tau and NfL have potential to fill key unmet needs for biomarkers in prion disease: as a secondary outcome for clinical trials (NfL and tau); for predicting onset in at-risk individuals (NfL); and as an accessible test for earlier identification of patients that may have CJD and require more definitive tests (NfL). Further studies should evaluate their performance directly in these specific roles.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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- Av författaren/redakt...
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Thompson, Andrew ...
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Anastasiadis, Pr ...
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Druyeh, Ronald
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Whitworth, Ines
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Nayak, Annapurna
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Nihat, Akin
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visa fler...
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Mok, Tze How
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Rudge, Peter
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Wadsworth, Jonat ...
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Rohrer, Jonathan
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Schott, Jonathan ...
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Heslegrave, Aman ...
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Zetterberg, Henr ...
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Collinge, John
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Jackson, Graham ...
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Mead, Simon
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Neurovetenskaper
- Artiklar i publikationen
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Molecular psychi ...
- Av lärosätet
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Göteborgs universitet