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A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer's disease

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dc.contributor.author Barthélemy, Nicolas R.
dc.contributor.author Li, Yan
dc.contributor.author Joseph-Mathurin, Nelly
dc.contributor.author Gordon, Brian A.
dc.contributor.author Hassenstab, Jason
dc.contributor.author Benzinger, Tammie L.S.
dc.contributor.author Buckles, Virginia
dc.contributor.author Fagan, Anne M.
dc.contributor.author Perrin, Richard J.
dc.contributor.author Goate, Alison M.
dc.contributor.author Morris, John C.
dc.contributor.author Karch, Celeste M.
dc.contributor.author Xiong, Chengjie
dc.contributor.author Allegri, Ricardo Francisco
dc.contributor.author Chrem Méndez, Patricio Alexis
dc.contributor.author Berman, Sarah B.
dc.contributor.author Ikeuchi, Takeshi
dc.contributor.author Mori, Hiroshi
dc.contributor.author Shimada, Hiroyuki
dc.contributor.author Shoji, Mikio
dc.contributor.author Suzuki, Kazushi
dc.contributor.author Noble, James M.
dc.contributor.author Farlow, Martin R.
dc.contributor.author Chhatwal, Jasmeer P.
dc.contributor.author Graff-Radford, Neill R.
dc.contributor.author Salloway, Stephen
dc.contributor.author Schofield, Peter R.
dc.contributor.author Masters, Colin L.
dc.contributor.author Martins, Ralph N.
dc.contributor.author O’Connor, Antoinette
dc.contributor.author Fox, Nick C.
dc.contributor.author Levin, Johannes
dc.contributor.author Jucker, Mathias
dc.contributor.author Gabelle, Audrey
dc.contributor.author Lehmann, Sylvain
dc.contributor.author Sato, Chihiro
dc.contributor.author Bateman, Randall J.
dc.contributor.author McDade, Eric
dc.contributor.author Dominantly Inherited Alzheimer Network
dc.date.accessioned 2020-11-10T13:58:51Z
dc.date.available 2020-11-10T13:58:51Z
dc.date.issued 2020-03
dc.identifier.citation Barthélemy, N.R., Li, Y., Joseph-Mathurin, N., Gordon, B.A., Hassenstab, J., Benzinger, T.L.S., Buckles, V., Fagan, A.M., Perrin, R.J., Goate, A.M., Morris, J.C., Karch, C.M., Xiong, C., Allegri, R., Mendez, P.C., Berman, S.B., Ikeuchi, T., Mori, H., Shimada, H., Shoji, M., Suzuki, K., Noble, J., Farlow, M., Chhatwal, J., Graff-Radford, N.R., Salloway, S., Schofield, P.R., Masters, C.L., Martins, R.N., O’Connor, A., Fox, N.C., Levin, J., Jucker, M., Gabelle, A., Lehmann, S., Sato, C., Bateman, R.J., McDade, E., 2020. A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer’s disease. Nat Med 26, 398–407. https://doi.org/10.1038/s41591-020-0781-z. en_US
dc.identifier.uri https://repositorio.fleni.org.ar/handle/123456789/226
dc.identifier.uri https://doi.org/10.1038/s41591-020-0781-z.
dc.description.abstract Development of tau-based therapies for Alzheimer's disease requires an understanding of the timing of disease-related changes in tau. We quantified the phosphorylation state at multiple sites of the tau protein in cerebrospinal fluid markers across four decades of disease progression in dominantly inherited Alzheimer's disease. We identified a pattern of tau staging where site-specific phosphorylation changes occur at different periods of disease progression and follow distinct trajectories over time. These tau phosphorylation state changes are uniquely associated with structural, metabolic, neurodegenerative and clinical markers of disease, and some (p-tau217 and p-tau181) begin with the initial increases in aggregate amyloid-β as early as two decades before the development of aggregated tau pathology. Others (p-tau205 and t-tau) increase with atrophy and hypometabolism closer to symptom onset. These findings provide insights into the pathways linking tau, amyloid-β and neurodegeneration, and may facilitate clinical trials of tau-based treatments. en_US
dc.language.iso eng en_US
dc.publisher Nature en_US
dc.rights info:eu-repo/semantics/openAccess
dc.rights.uri https://creativecommons.org/licenses/by/2.5/ar/
dc.subject Enfermedad de Alzheimer en_US
dc.subject Alzheimer Disease en_US
dc.title A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer's disease en_US
dc.title.alternative A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer’s disease. en_US
dc.type info:eu-repo/semantics/publishedVersion
dc.type info:eu-repo/semantics/article en_US
dc.description.fil Fil: Allegri, Ricardo Francisco. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría; Argentina.
dc.description.fil Fil: Chrem Méndez, Patricio Alexis. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría. Centro de Memoria y Envejecimiento; Argentina
dc.description.fil Fil: Barthélemy, Nicolas R. Washington University School of Medicine. Department of Neurology; Estados Unidos.
dc.description.fil Fil: Li, Yan. Washington University School of Medicine. Department of Neurology; Estados Unidos. Washington University School of Medicine. Division of Biostatistics; Estados Unidos.
dc.description.fil Fil: Joseph-Mathurin, Nelly. Washington University School of Medicine. Department of Radiology; Estados Unidos.
dc.description.fil Fil: Gordon, Brian A. Washington University School of Medicine. Department of Radiology; Estados Unidos.
dc.description.fil Fil: Hassenstab, Jason. Washington University School of Medicine. Department of Neurology; Estados Unidos.
dc.description.fil Fil: Benzinger, Tammie L.S. Washington University School of Medicine. Department of Radiology; Estados Unidos.
dc.description.fil Fil: Buckles, Virginia. Washington University School of Medicine. Department of Neurology; Estados Unidos.
dc.description.fil Fil: Fagan, Anne M. Washington University School of Medicine. Department of Neurology; Estados Unidos.
dc.description.fil Fil: Perrin, Richard J. Washington University School of Medicine. Department of Pathology; Estados Unidos.
dc.description.fil Fil: Goate, Alison M. Icahn School of Medicine at Mount Sinai. Department of Neuroscience; Estados Unidos.
dc.description.fil Fil: Morris, John C. Washington University School of Medicine. Department of Neurology; Estados Unidos.
dc.description.fil Fil: Karch, Celeste M. Washington University School of Medicine. Department of Psychiatry; Estados Unidos.
dc.description.fil Fil: Xiong, Chengjie. Washington University School of Medicine. Division of Biostatistics; Estados Unidos.
dc.description.fil Fil: Berman, Sarah B. University of Pittsburgh School of Medicine; Estados Unidos.
dc.description.fil Fil: Ikeuchi, Takeshi. Niigata University; Japón.
dc.description.fil Fil: Mori, Hiroshi. Osaka City University; Japón.
dc.description.fil Fil: Shimada, Hiroyuki. Osaka City University; Japón.
dc.description.fil Fil: Shoji, Mikio. Hirosaki University; Japón.
dc.description.fil Fil: Suzuki, Kazushi. Tokyo University; Japón.
dc.description.fil Fil: Noble, James. Columbia University. College of Physicians and Surgeons; Estados Unidos.
dc.description.fil Fil: Farlow, Martin R. Indiana University, Indianapolis. Department of Neurology; Estados Unidos.
dc.description.fil Fil: Chhatwal, Jasmeer P. Massachusetts General Hospital; Estados Unidos. Harvard Medical School; Estados Unidos.
dc.type.snrd info:ar-repo/semantics/artículo es_ES


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