Differential roles of Aβ42/40, p-tau231 and p-tau217 for Alzheimer’s trial selection and disease monitoring
Nicholas J. Ashton,Shorena Janelidze,Niklas Mattsson-Carlgren,Alexa Pichet Binette,Olof Strandberg,Wagner Scheeren Brum,Thomas K. Karikari,Fernándo González-Ortiz,Guglielmo Di Molfetta,Francisco J. Meda,Erin M. Jonaitis,Rebecca L. Koscik,Karly Alex Cody,Tobey J. Betthauser,Yan Li,Eugeen Vanmechelen,Sebastian Palmqvist,Erik Stomrud,Randall J. Bateman,Henrik Zetterberg,Sterling C. Johnson,Kaj Blennow,Oskar Hansson +22 more
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TLDR
The selective longitudinal increase of p-tau217 and its associations with cognitive decline and atrophy was confirmed in an independent cohort (Wisconsin Registry for Alzheimer's Prevention) as discussed by the authors .Abstract:
Abstract Blood biomarkers indicative of Alzheimer’s disease (AD) pathology are altered in both preclinical and symptomatic stages of the disease. Distinctive biomarkers may be optimal for the identification of AD pathology or monitoring of disease progression. Blood biomarkers that correlate with changes in cognition and atrophy during the course of the disease could be used in clinical trials to identify successful interventions and thereby accelerate the development of efficient therapies. When disease-modifying treatments become approved for use, efficient blood-based biomarkers might also inform on treatment implementation and management in clinical practice. In the BioFINDER-1 cohort, plasma phosphorylated (p)-tau231 and amyloid-β42/40 ratio were more changed at lower thresholds of amyloid pathology. Longitudinally, however, only p-tau217 demonstrated marked amyloid-dependent changes over 4–6 years in both preclinical and symptomatic stages of the disease, with no such changes observed in p-tau231, p-tau181, amyloid-β42/40, glial acidic fibrillary protein or neurofilament light. Only longitudinal increases of p-tau217 were also associated with clinical deterioration and brain atrophy in preclinical AD. The selective longitudinal increase of p-tau217 and its associations with cognitive decline and atrophy was confirmed in an independent cohort (Wisconsin Registry for Alzheimer’s Prevention). These findings support the differential association of plasma biomarkers with disease development and strongly highlight p-tau217 as a surrogate marker of disease progression in preclinical and prodromal AD, with impact for the development of new disease-modifying treatments. read more
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Specific associations between plasma biomarkers and postmortem amyloid plaque and tau tangle loads
Gemma Salvadó,Rik Ossenkoppele,Nicholas J. Ashton,Thomas G. Beach,Geidy E. Serrano,Eric M. Reiman,Henrik Zetterberg,Niklas Mattsson-Carlgren,Shorena Janelidze,Kaj Blennow,Oskar Hansson +10 more
TL;DR: The authors investigated independent associations between multiple plasma biomarkers and neuropathologic measures of amyloid and tau and found that highperforming assays of plasma p−tau217 and Aβ42/40 might be an optimal combination to assess Alzheimer's-related pathology in vivo.
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Plasma phospho-tau in Alzheimer’s disease: towards diagnostic and therapeutic trial applications
Fernándo González-Ortiz,P. Kac,Wagner Scheeren Brum,Henrik Zetterberg,Kaj Blennow,Thomas K. Karikari +5 more
TL;DR: In this paper , the authors provide an update on the diagnostic and prognostic performances of plasma p-tau, and their associations with in vivo and autopsy-verified diagnosis and pathological hallmarks.
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CSF tau phosphorylation occupancies at T217 and T205 represent improved biomarkers of amyloid and tau pathology in Alzheimer’s disease
Nicolas R. Barthélemy,Benjamin Saef,Yan Li,Brian A. Gordon,Yingxin He,Kanta Horie,Erik Stomrud,Gemma Salvadó,Shorena Janelidze,Chihiro Sato,Vitaliy Ovod,Rachel L. Henson,Anne M. Fagan,Tammie L.S. Benzinger,Chengjie Xiong,John C. Morris,Oskar Hansson,Randall J. Bateman,Suzanne E. Schindler +18 more
TL;DR: In this paper , the authors used mass spectrometry to measure concentrations of nine phosphorylated and five nonphosphorylated tau species and phosphorylation occupancies at ten sites.
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Plasma biomarkers for neurodegenerative disorders: ready for prime time?
TL;DR: In this paper , a review of the current evidence for and against the immediate use of plasma biomarkers in clinical care is presented, highlighting the issues around thresholds, comorbidities and diverse populations to be addressed.
Journal ArticleDOI
Mass spectrometric simultaneous quantification of tau species in plasma shows differential associations with amyloid and tau pathologies
Laia Montoliu-Gaya,Andrea Lessa Benedet,Cecile Tissot,Agathe Vrillon,Nicholas J. Ashton,Wagner Scheeren Brum,Juan Lantero-Rodriguez,Jenna Stevenson,Johanna Nilsson,Mathias Sauer,Nesrine Rahmouni,Gunnar Brinkmalm,Firoza Z. Lussier,Tharick A. Pascoal,Ingmar Skoog,Silke Kern,Henrik Zetterberg,Claire Paquet,Johan Gobom,Pedro Rosa-Neto,Kaj Blennow +20 more
TL;DR: In this article , the authors employed an immunoprecipitation mass spectrometry method to simultaneously quantify six phosphorylated (p-tau181, ptau199, p-tAU199), six non-phosphorylated tau peptides, and two non-plasminar peptides in total of 214 participants from the Paris Lariboisière and Translational Biomarkers of Aging and Dementia cohorts.
References
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Plasma P-tau181 in Alzheimer’s disease: relationship to other biomarkers, differential diagnosis, neuropathology and longitudinal progression to Alzheimer’s dementia
Shorena Janelidze,Niklas Mattsson,Sebastian Palmqvist,Ruben Smith,Thomas G. Beach,Geidy E. Serrano,Xiyun Chai,Nicholas K. Proctor,Udo Eichenlaub,Henrik Zetterberg,Kaj Blennow,Kaj Blennow,Eric M. Reiman,Erik Stomrud,Jeffrey L. Dage,Oskar Hansson +15 more
TL;DR: Plasma P-tau18 level increased with progression of Alzheimer’s disease (AD) and differentiated AD dementia from other neurodegenerative diseases, supporting its further development as a blood-based biomarker for AD.
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Blood phosphorylated tau 181 as a biomarker for Alzheimer's disease: a diagnostic performance and prediction modelling study using data from four prospective cohorts.
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TL;DR: Blood p-tau181 can predict tau and amyloid β pathologies, differentiate Alzheimer's disease from other neurodegenerative disorders, and identify Alzheimer's Disease across the clinical continuum.
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William E. Klunk,William E. Klunk,Robert A. Koeppe,Julie C. Price,Tammie L.S. Benzinger,Tammie L.S. Benzinger,Michael D. Devous,William J. Jagust,Keith A. Johnson,Chester A. Mathis,Davneet S. Minhas,Michael J. Pontecorvo,Christopher C. Rowe,Daniel Skovronsky,Mark A. Mintun +14 more
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Association of plasma neurofilament light with neurodegeneration in patients with Alzheimer disease
TL;DR: Plasma NFL is associated with AD diagnosis and with cognitive, biochemical, and imaging hallmarks of the disease and implies a potential usefulness for plasma NFL as a noninvasive biomarker in AD.
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Discriminative Accuracy of Plasma Phospho-tau217 for Alzheimer Disease vs Other Neurodegenerative Disorders.
Sebastian Palmqvist,Shorena Janelidze,Yakeel T. Quiroz,Yakeel T. Quiroz,Henrik Zetterberg,Francisco Lopera,Erik Stomrud,Yi Su,Yinghua Chen,Geidy E. Serrano,Antoine Leuzy,Niklas Mattsson-Carlgren,Olof Strandberg,Ruben Smith,Andrés Villegas,Diego Sepulveda-Falla,Diego Sepulveda-Falla,Xiyun Chai,Nicholas K. Proctor,Thomas G. Beach,Kaj Blennow,Kaj Blennow,Jeffrey L. Dage,Eric M. Reiman,Oskar Hansson +24 more
TL;DR: Plasma P-tau217 levels were significantly greater among PSEN1 mutation carriers, compared with noncarriers, from approximately 25 years and older, which is 20 years prior to estimated onset of MCI among mutation carriers.