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
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/161441
Ver los metadatos del registro completo
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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 Técnicas2025-10-15T15:26:53Zoai: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:34982025-10-15 15:26:53.464CONICET 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 |
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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 |
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eng |
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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 |
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Nature Publishing Group |
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Nature Publishing Group |
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