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CSF p-tau205: a bio...
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Lantero Rodriguez, JuanGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
(author)
CSF p-tau205: a biomarker of tau pathology in Alzheimer's disease.
- Article/chapterEnglish2024
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LIBRIS-ID:oai:gup.ub.gu.se/333357
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https://gup.ub.gu.se/publication/333357URI
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https://doi.org/10.1007/s00401-023-02659-wDOI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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Post-mortem staging of Alzheimer's disease (AD) neurofibrillary pathology is commonly performed by immunohistochemistry using AT8 antibody for phosphorylated tau (p-tau) at positions 202/205. Thus, quantification of p-tau205 and p-tau202 in cerebrospinal fluid (CSF) should be more reflective of neurofibrillary tangles in AD than other p-tau epitopes. We developed two novel Simoa immunoassays for CSF p-tau205 and p-tau202 and measured these phosphorylations in three independent cohorts encompassing the AD continuum, non-AD cases and cognitively unimpaired participants: a discovery cohort (n=47), an unselected clinical cohort (n=212) and a research cohort well-characterized by fluid and imaging biomarkers (n=262). CSF p-tau205 increased progressively across the AD continuum, while CSF p-tau202 was increased only in AD and amyloid(Aβ) and tau pathology positive (A+T+) cases (P<0.01). In A+cases, CSF p-tau205 and p-tau202 showed stronger associations with tau-PET (rSp205=0.67, rSp202=0.45) than Aβ-PET (rSp205=0.40, rSp202=0.09). CSF p-tau205 increased gradually across tau-PET Braak stages (P<0.01), whereas p-tau202 only increased in Braak V-VI (P<0.0001). Both showed stronger regional associations with tau-PET than with Aβ-PET, and CSF p-tau205 was significantly associated with Braak V-VI tau-PET regions. When assessing the contribution of Aβ and tau pathologies (indexed by PET) to CSF p-tau205 and p-tau202 variance, tau pathology was found to be the most prominent contributor in both cases (CSF p-tau205: R2=69.7%; CSF p-tau202: R2=85.6%) Both biomarkers associated with brain atrophy measurements globally (rSp205=-0.36, rSp202=-0.33) and regionally, and correlated with cognition (rSp205=-0.38/-0.40, rSp202=-0.20/-0.29). In conclusion, we report the first high-throughput CSF p-tau205 immunoassay for the in vivo quantification of tau pathology in AD, and a potentially cost-effective alternative to tau-PET in clinical settings and clinical trials.
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Montoliu-Gaya, LaiaGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xmonla
(author)
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Lessa Benedet, AndréaGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xlesan
(author)
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Vrillon, Agathe
(author)
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Dumurgier, Julien
(author)
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Cognat, Emmanuel
(author)
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Brum, Wagner S.Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
(author)
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Rahmouni, Nesrine
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Stevenson, Jenna
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Servaes, Stijn
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Therriault, Joseph
(author)
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Becker, Bruno,1961Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xbecbr
(author)
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Brinkmalm, GunnarGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xbrigu
(author)
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Snellman, AnniinaGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xsnela
(author)
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Huber, Hanna,1989Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xhubha
(author)
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Kvartsberg, Hlin,1987Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xjohhl
(author)
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Ashton, Nicholas J.Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xashtn
(author)
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Zetterberg, Henrik,1973Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xzethe
(author)
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Paquet, Claire
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Rosa-Neto, Pedro
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Blennow, Kaj,1958Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xbleka
(author)
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Göteborgs universitetInstitutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
(creator_code:org_t)
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In:Acta neuropathologica147:11432-0533
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Cognat, Emmanuel
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Brum, Wagner S.
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Brinkmalm, Gunna ...
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Snellman, Anniin ...
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Huber, Hanna, 19 ...
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Kvartsberg, Hlin ...
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