Sökning: id:"swepub:oai:gup.ub.gu.se/315995" >
N-terminal and mid-...
N-terminal and mid-region tau fragments as fluid biomarkers in neurological diseases.
-
- Snellman, Anniina (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
-
- Lantero Rodriguez, Juan (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
-
Emeršič, Andreja (författare)
-
visa fler...
-
Vrillon, Agathe (författare)
-
- Karikari, Thomas (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
-
- Ashton, Nicholas J. (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
-
- Gregorič Kramberger, Milica (författare)
- Karolinska Institutet
-
Čučnik, Saša (författare)
-
Paquet, Claire (författare)
-
Rot, Uroš (författare)
-
- 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
-
- Blennow, Kaj, 1958 (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
-
visa färre...
-
(creator_code:org_t)
- 2022-07-27
- 2022
- Engelska.
-
Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 145:8, s. 2834-2848
- Relaterad länk:
-
https://gup.ub.gu.se...
-
visa fler...
-
https://doi.org/10.1...
-
http://kipublication...
-
visa färre...
Abstract
Ämnesord
Stäng
- Brain-derived tau secreted into CSF and blood consists of different N-terminal and mid-domain fragments, which may have a differential temporal course and thus, biomarker potential across the Alzheimer's disease continuum or in other neurological diseases. While current clinically validated total-tau (t-tau) assays target mid-domain epitopes, comparison of these assays with new biomarkers targeting N-terminal epitopes using the same analytical platform may be important to increase the understanding of tau pathophysiology. We developed three t-tau immunoassays targeting specific N-terminal (NTA and NTB t-tau) or mid-region (MR t-tau) epitopes, using single molecule array technology. After analytical validation, the diagnostic performance of these biomarkers was evaluated in CSF and compared with the Innotest t-tau (and as proof of concept, with N-p-tau181 and N-p-tau217) in three clinical cohorts (n = 342 total). The cohorts included participants across the Alzheimer's disease continuum (n = 276), other dementia (n = 22), Creutzfeldt-Jakob disease (n = 24), acute neurological disorders (n = 18) and progressive supranuclear palsy (n = 22). Furthermore, we evaluated all three new t-tau biomarkers in plasma (n = 44) and replicated promising findings with NTA t-tau in another clinical cohort (n = 50). In CSF, all t-tau biomarkers were increased in Alzheimer's disease compared with controls (P < 0.0001) and correlated with each other (rs = 0.53-0.95). NTA and NTB t-tau, but not other t-tau assays, distinguished amyloid-positive and amyloid-negative mild cognitive impairment with high accuracies (AUCs 84% and 82%, P < 0.001) matching N-p-tau217 (AUC 83%; DeLong test P = 0.93 and 0.88). All t-tau assays were excellent in differentiating Alzheimer's disease from other dementias (P < 0.001, AUCs 89-100%). In Creutzfeldt-Jakob disease and acute neurological disorders, N-terminal t-tau biomarkers had significantly higher fold changes versus controls in CSF (45-133-fold increase) than Innotest or MR t-tau (11-42-fold increase, P < 0.0001 for all). In progressive supranuclear palsy, CSF concentrations of all t-tau biomarkers were similar to those in controls. Plasma NTA t-tau concentrations were increased in Alzheimer's disease compared with controls in two independent cohorts (P = 0.0056 and 0.0033) while Quanterix t-tau performed poorly (P = 0.55 and 0.44). Taken together, N-terminal-directed CSF t-tau biomarkers increase ahead of standard t-tau alternatives in the Alzheimer's disease continuum, increase to higher degrees in Creutzfeldt-Jakob disease and acute neurological diseases and show better potential than Quanterix t-tau as Alzheimer's disease blood biomarkers. For progressive supranuclear palsy, other tau biomarkers should still be investigated.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- Alzheimer’s disease
- biomarker
- cerebrospinal fluid
- plasma
- tau
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Snellman, Anniin ...
-
Lantero Rodrigue ...
-
Emeršič, Andreja
-
Vrillon, Agathe
-
Karikari, Thomas
-
Ashton, Nicholas ...
-
visa fler...
-
Gregorič Kramber ...
-
Čučnik, Saša
-
Paquet, Claire
-
Rot, Uroš
-
Zetterberg, Henr ...
-
Blennow, Kaj, 19 ...
-
visa färre...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Medicinska och f ...
-
och Neurovetenskaper
- Artiklar i publikationen
-
Brain : a journa ...
-
Brain
- Av lärosätet
-
Göteborgs universitet
-
Karolinska Institutet