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

Autores
Barthélemy, Nicolas R.; Li, Yan; Joseph Mathurin, Nelly; Gordon, Brian A.; Hassenstab, Jason; Benzinger, Tammie L. S.; Buckles, Virginia; Fagan, Anne M.; Perrin, Richard J.; Goate, Alison M.; Morris, John C.; Karch, Celeste M.; Xiong, Chengjie; Allegri, Ricardo Francisco; Chrem Mendez, Patricio Alexis; Berman, Sarah B.; Ikeuchi, Takeshi; Mori, Hiroshi; Shimada, Hiroyuki; Shoji, Mikio; Suzuki, Kazushi; Noble, James; Farlow, Martin; Chhatwal, Jasmeer; Graff Radford, Neill R.; Salloway, Stephen; Schofield, Peter R.; Masters, Colin; Martins, Ralph N.; O'Connor, Antoinette
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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 sitespecific 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 taubased treatments.
Fil: Barthélemy, Nicolas R.. Washington University in St. Louis; Estados Unidos
Fil: Li, Yan. Washington University in St. Louis; Estados Unidos
Fil: Joseph Mathurin, Nelly. Washington University in St. Louis; Estados Unidos
Fil: Gordon, Brian A.. Washington University in St. Louis; Estados Unidos
Fil: Hassenstab, Jason. Washington University in St. Louis; Estados Unidos
Fil: Benzinger, Tammie L. S.. Washington University in St. Louis; Estados Unidos
Fil: Buckles, Virginia. Washington University in St. Louis; Estados Unidos
Fil: Fagan, Anne M.. Washington University in St. Louis; Estados Unidos
Fil: Perrin, Richard J.. Washington University in St. Louis; Estados Unidos
Fil: Goate, Alison M.. Icahn School Of Medicine At Mount Sinai; Estados Unidos
Fil: Morris, John C.. Washington University in St. Louis; Estados Unidos
Fil: Karch, Celeste M.. Washington University in St. Louis; Estados Unidos
Fil: Xiong, Chengjie. Washington University in St. Louis; Estados Unidos
Fil: Allegri, Ricardo Francisco. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Chrem Mendez, Patricio Alexis. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Berman, Sarah B.. Univeristy of Pittsburgh. School of Medicine; Estados Unidos
Fil: Ikeuchi, Takeshi. Niigata University; Japón
Fil: Mori, Hiroshi. Osaka City University; Japón
Fil: Shimada, Hiroyuki. Osaka City University; Japón
Fil: Shoji, Mikio. Hirosaki University; Japón
Fil: Suzuki, Kazushi. The University Of Tokyo; Japón
Fil: Noble, James. Columbia University; Estados Unidos
Fil: Farlow, Martin. Indiana University; Estados Unidos
Fil: Chhatwal, Jasmeer. Harvard Medical School. Department of Medicine. Massachusetts General Hospital; Estados Unidos
Fil: Graff Radford, Neill R.. Mayo Clinic Cancer Center; Estados Unidos
Fil: Salloway, Stephen. University Brown; Estados Unidos. Butler Hospital; Estados Unidos
Fil: Schofield, Peter R.. University of New South Wales; Australia. Neuroscience Research Australia; Australia
Fil: Masters, Colin. University of Melbourne; Australia. The Florey Institute Of Neuroscience And Mental Health; Australia
Fil: Martins, Ralph N.. Edith Cowan University; Australia
Fil: O'Connor, Antoinette. University College London; Estados Unidos
Materia
ALZHEIMER
Biomarkers
Tau
DIAN
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/161441

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spelling A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer’s diseaseBarthélemy, Nicolas R.Li, YanJoseph Mathurin, NellyGordon, Brian A.Hassenstab, JasonBenzinger, Tammie L. S.Buckles, VirginiaFagan, Anne M.Perrin, Richard J.Goate, Alison M.Morris, John C.Karch, Celeste M.Xiong, ChengjieAllegri, Ricardo FranciscoChrem Mendez, Patricio AlexisBerman, Sarah B.Ikeuchi, TakeshiMori, HiroshiShimada, HiroyukiShoji, MikioSuzuki, KazushiNoble, JamesFarlow, MartinChhatwal, JasmeerGraff Radford, Neill R.Salloway, StephenSchofield, Peter R.Masters, ColinMartins, Ralph N.O'Connor, AntoinetteALZHEIMERBiomarkersTauDIANhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Development 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 sitespecific 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 taubased treatments.Fil: Barthélemy, Nicolas R.. Washington University in St. Louis; Estados UnidosFil: Li, Yan. Washington University in St. Louis; Estados UnidosFil: Joseph Mathurin, Nelly. Washington University in St. Louis; Estados UnidosFil: Gordon, Brian A.. Washington University in St. Louis; Estados UnidosFil: Hassenstab, Jason. Washington University in St. Louis; Estados UnidosFil: Benzinger, Tammie L. S.. Washington University in St. Louis; Estados UnidosFil: Buckles, Virginia. Washington University in St. Louis; Estados UnidosFil: Fagan, Anne M.. Washington University in St. Louis; Estados UnidosFil: Perrin, Richard J.. Washington University in St. Louis; Estados UnidosFil: Goate, Alison M.. Icahn School Of Medicine At Mount Sinai; Estados UnidosFil: Morris, John C.. Washington University in St. Louis; Estados UnidosFil: Karch, Celeste M.. Washington University in St. Louis; Estados UnidosFil: Xiong, Chengjie. Washington University in St. Louis; Estados UnidosFil: Allegri, Ricardo Francisco. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chrem Mendez, Patricio Alexis. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Berman, Sarah B.. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Ikeuchi, Takeshi. Niigata University; JapónFil: Mori, Hiroshi. Osaka City University; JapónFil: Shimada, Hiroyuki. Osaka City University; JapónFil: Shoji, Mikio. Hirosaki University; JapónFil: Suzuki, Kazushi. The University Of Tokyo; JapónFil: Noble, James. Columbia University; Estados UnidosFil: Farlow, Martin. Indiana University; Estados UnidosFil: Chhatwal, Jasmeer. Harvard Medical School. Department of Medicine. Massachusetts General Hospital; Estados UnidosFil: Graff Radford, Neill R.. Mayo Clinic Cancer Center; Estados UnidosFil: Salloway, Stephen. University Brown; Estados Unidos. Butler Hospital; Estados UnidosFil: Schofield, Peter R.. University of New South Wales; Australia. Neuroscience Research Australia; AustraliaFil: Masters, Colin. University of Melbourne; Australia. The Florey Institute Of Neuroscience And Mental Health; AustraliaFil: Martins, Ralph N.. Edith Cowan University; AustraliaFil: O'Connor, Antoinette. University College London; Estados UnidosNature Publishing Group2020-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/161441Barthélemy, Nicolas R.; Li, Yan; Joseph Mathurin, Nelly; Gordon, Brian A.; Hassenstab, Jason; et al.; A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer’s disease; Nature Publishing Group; Nature Medicine; 26; 3; 3-2020; 398-4071078-89561546-170XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41591-020-0781-zinfo:eu-repo/semantics/altIdentifier/doi/10.1038/s41591-020-0781-zinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:29:40Zoai:ri.conicet.gov.ar:11336/161441instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:29:41.21CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer’s disease
title A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer’s disease
spellingShingle A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer’s disease
Barthélemy, Nicolas R.
ALZHEIMER
Biomarkers
Tau
DIAN
title_short A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer’s disease
title_full A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer’s disease
title_fullStr A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer’s disease
title_full_unstemmed A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer’s disease
title_sort A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer’s disease
dc.creator.none.fl_str_mv Barthélemy, Nicolas R.
Li, Yan
Joseph Mathurin, Nelly
Gordon, Brian A.
Hassenstab, Jason
Benzinger, Tammie L. S.
Buckles, Virginia
Fagan, Anne M.
Perrin, Richard J.
Goate, Alison M.
Morris, John C.
Karch, Celeste M.
Xiong, Chengjie
Allegri, Ricardo Francisco
Chrem Mendez, Patricio Alexis
Berman, Sarah B.
Ikeuchi, Takeshi
Mori, Hiroshi
Shimada, Hiroyuki
Shoji, Mikio
Suzuki, Kazushi
Noble, James
Farlow, Martin
Chhatwal, Jasmeer
Graff Radford, Neill R.
Salloway, Stephen
Schofield, Peter R.
Masters, Colin
Martins, Ralph N.
O'Connor, Antoinette
author Barthélemy, Nicolas R.
author_facet Barthélemy, Nicolas R.
Li, Yan
Joseph Mathurin, Nelly
Gordon, Brian A.
Hassenstab, Jason
Benzinger, Tammie L. S.
Buckles, Virginia
Fagan, Anne M.
Perrin, Richard J.
Goate, Alison M.
Morris, John C.
Karch, Celeste M.
Xiong, Chengjie
Allegri, Ricardo Francisco
Chrem Mendez, Patricio Alexis
Berman, Sarah B.
Ikeuchi, Takeshi
Mori, Hiroshi
Shimada, Hiroyuki
Shoji, Mikio
Suzuki, Kazushi
Noble, James
Farlow, Martin
Chhatwal, Jasmeer
Graff Radford, Neill R.
Salloway, Stephen
Schofield, Peter R.
Masters, Colin
Martins, Ralph N.
O'Connor, Antoinette
author_role author
author2 Li, Yan
Joseph Mathurin, Nelly
Gordon, Brian A.
Hassenstab, Jason
Benzinger, Tammie L. S.
Buckles, Virginia
Fagan, Anne M.
Perrin, Richard J.
Goate, Alison M.
Morris, John C.
Karch, Celeste M.
Xiong, Chengjie
Allegri, Ricardo Francisco
Chrem Mendez, Patricio Alexis
Berman, Sarah B.
Ikeuchi, Takeshi
Mori, Hiroshi
Shimada, Hiroyuki
Shoji, Mikio
Suzuki, Kazushi
Noble, James
Farlow, Martin
Chhatwal, Jasmeer
Graff Radford, Neill R.
Salloway, Stephen
Schofield, Peter R.
Masters, Colin
Martins, Ralph N.
O'Connor, Antoinette
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ALZHEIMER
Biomarkers
Tau
DIAN
topic ALZHEIMER
Biomarkers
Tau
DIAN
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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 sitespecific 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 taubased treatments.
Fil: Barthélemy, Nicolas R.. Washington University in St. Louis; Estados Unidos
Fil: Li, Yan. Washington University in St. Louis; Estados Unidos
Fil: Joseph Mathurin, Nelly. Washington University in St. Louis; Estados Unidos
Fil: Gordon, Brian A.. Washington University in St. Louis; Estados Unidos
Fil: Hassenstab, Jason. Washington University in St. Louis; Estados Unidos
Fil: Benzinger, Tammie L. S.. Washington University in St. Louis; Estados Unidos
Fil: Buckles, Virginia. Washington University in St. Louis; Estados Unidos
Fil: Fagan, Anne M.. Washington University in St. Louis; Estados Unidos
Fil: Perrin, Richard J.. Washington University in St. Louis; Estados Unidos
Fil: Goate, Alison M.. Icahn School Of Medicine At Mount Sinai; Estados Unidos
Fil: Morris, John C.. Washington University in St. Louis; Estados Unidos
Fil: Karch, Celeste M.. Washington University in St. Louis; Estados Unidos
Fil: Xiong, Chengjie. Washington University in St. Louis; Estados Unidos
Fil: Allegri, Ricardo Francisco. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Chrem Mendez, Patricio Alexis. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Berman, Sarah B.. Univeristy of Pittsburgh. School of Medicine; Estados Unidos
Fil: Ikeuchi, Takeshi. Niigata University; Japón
Fil: Mori, Hiroshi. Osaka City University; Japón
Fil: Shimada, Hiroyuki. Osaka City University; Japón
Fil: Shoji, Mikio. Hirosaki University; Japón
Fil: Suzuki, Kazushi. The University Of Tokyo; Japón
Fil: Noble, James. Columbia University; Estados Unidos
Fil: Farlow, Martin. Indiana University; Estados Unidos
Fil: Chhatwal, Jasmeer. Harvard Medical School. Department of Medicine. Massachusetts General Hospital; Estados Unidos
Fil: Graff Radford, Neill R.. Mayo Clinic Cancer Center; Estados Unidos
Fil: Salloway, Stephen. University Brown; Estados Unidos. Butler Hospital; Estados Unidos
Fil: Schofield, Peter R.. University of New South Wales; Australia. Neuroscience Research Australia; Australia
Fil: Masters, Colin. University of Melbourne; Australia. The Florey Institute Of Neuroscience And Mental Health; Australia
Fil: Martins, Ralph N.. Edith Cowan University; Australia
Fil: O'Connor, Antoinette. University College London; Estados Unidos
description 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 sitespecific 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 taubased treatments.
publishDate 2020
dc.date.none.fl_str_mv 2020-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/161441
Barthélemy, Nicolas R.; Li, Yan; Joseph Mathurin, Nelly; Gordon, Brian A.; Hassenstab, Jason; et al.; A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer’s disease; Nature Publishing Group; Nature Medicine; 26; 3; 3-2020; 398-407
1078-8956
1546-170X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/161441
identifier_str_mv Barthélemy, Nicolas R.; Li, Yan; Joseph Mathurin, Nelly; Gordon, Brian A.; Hassenstab, Jason; et al.; A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer’s disease; Nature Publishing Group; Nature Medicine; 26; 3; 3-2020; 398-407
1078-8956
1546-170X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41591-020-0781-z
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41591-020-0781-z
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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