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Novel tau biomarkers phosphorylated at T181, T217 or T231 rise in the initial stages of the preclinical Alzheimer's continuum when only subtle changes in Aβ pathology are detected.
- Suárez-Calvet, Marc (author)
-
- Karikari, Thomas (author)
- 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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- Ashton, Nicholas J. (author)
- 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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- Milà-Alomà, Marta (author)
- Gispert, Juan Domingo (author)
- Salvadó, Gemma (author)
- Minguillon, Carolina (author)
- Fauria, Karine (author)
- Shekari, Mahnaz (author)
- Grau-Rivera, Oriol (author)
- Arenaza-Urquijo, Eider M (author)
- Sala-Vila, Aleix (author)
- Sánchez-Benavides, Gonzalo (author)
- González-de-Echávarri, José Maria (author)
- Kollmorgen, Gwendlyn (author)
- Stoops, Erik (author)
- Vanmechelen, Eugeen (author)
- Molinuevo, José Luis (author)
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- (creator_code:org_t)
- 2020-11-10
- 2020
- English.
- In: EMBO molecular medicine. - : EMBO. - 1757-4684 .- 1757-4676. ; 12:12
- Journal article (peer-reviewed)
Abstract
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- In Alzheimer's disease (AD), tau phosphorylation in the brain and its subsequent release into cerebrospinal fluid (CSF) and blood is a dynamic process that changes during disease evolution. The main aim of our study was to characterize the pattern of changes in phosphorylated tau (p-tau) in the preclinical stage of the Alzheimer's continuum. We measured three novel CSF p-tau biomarkers, phosphorylated at threonine-181 and threonine-217 with an N-terminal partner antibody and at threonine-231 with a mid-region partner antibody. These were compared with an automated mid-region p-tau181 assay (Elecsys) as the gold standard p-tau measure. We demonstrate that these novel p-tau biomarkers increase more prominently in preclinical Alzheimer, when only subtle changes of amyloid-β (Aβ) pathology are detected, and can accurately differentiate Aβ-positive from Aβ-negative cognitively unimpaired individuals. Moreover, we show that the novel plasma N-terminal p-tau181 biomarker is mildly but significantly increased in the preclinical stage. Our results support the idea that early changes in neuronal tau metabolism in preclinical Alzheimer, likely in response to Aβ exposure, can be detected with these novel p-tau assays.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
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- art (subject category)
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