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dc.contributor.author
Llibre Guerra, Jorge J.
dc.contributor.author
Li, Yan
dc.contributor.author
Schindler, Suzanne E.
dc.contributor.author
Gordon, Brian A.
dc.contributor.author
Fagan, Anne M.
dc.contributor.author
Morris, John C.
dc.contributor.author
Benzinger, Tammie L. S.
dc.contributor.author
Hassenstab, Jason
dc.contributor.author
Wang, Guoqiao
dc.contributor.author
Allegri, Ricardo Francisco
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dc.contributor.author
Berman, Sarah B.
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Chhatwal, Jasmeer
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Farlow, Martin R.
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Holtzman, David M.
dc.contributor.author
Jucker, Mathias
dc.contributor.author
Levin, Johannes
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Noble, James M.
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Salloway, Stephen
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Schofield, Peter
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Karch, Celeste
dc.contributor.author
Fox, Nick C.
dc.contributor.author
Xiong, Chengjie
dc.contributor.author
Bateman, Randall J.
dc.contributor.author
McDade, Eric
dc.date.available
2022-07-26T11:34:53Z
dc.date.issued
2019-12
dc.identifier.citation
Llibre Guerra, Jorge J.; Li, Yan; Schindler, Suzanne E.; Gordon, Brian A.; Fagan, Anne M.; et al.; Association of Longitudinal Changes in Cerebrospinal Fluid Total Tau and Phosphorylated Tau 181 and Brain Atrophy with Disease Progression in Patients with Alzheimer Disease; American Medical Association; JAMA Network Open; 2; 12; 12-2019; 1-14
dc.identifier.issn
2574-3805
dc.identifier.uri
http://hdl.handle.net/11336/163113
dc.description.abstract
The amyloid/tau/neurodegeneration (A/T/N) framework uses cerebrospinal fluid (CSF) levels of total tau (tTau) as a marker of neurodegeneration and CSF levels of phosphorylated tau 181 (pTau181) as a marker of tau tangles. However, it is unclear whether CSF levels of tTau and pTau181 have similar or different trajectories over the course of Alzheimer disease. Objectives: To examine the rates of change in CSF levels of tTau and pTau181 across the Alzheimer disease course and how the rates of change are associated with brain atrophy as measured by magnetic resonance imaging. Design, Setting, and Participants: This cohort study was set in tertiary research clinics. Each participant was a member of a pedigree with a known mutation for dominantly inherited Alzheimer disease. Participants were divided into 3 groups on the basis of the presence of a mutation and their Clinical Dementia Rating score. Data analysis was performed in June 2019. Main Outcomes and Measures: Rates of change of CSF tTau and pTau181 levels and their association with the rate of change of brain volume. Results: Data from 465 participants (283 mutation carriers and 182 noncarriers) were analyzed. The mean (SD) age of the cohort was 37.8 (11.3) years, and 262 (56.3%) were women. The mean (SD) follow-up duration was 2.7 (1.5) years. Two or more longitudinal CSF and magnetic resonance imaging assessments were available for 160 and 247 participants, respectively. Sixty-five percent of mutation carriers (183) did not have symptoms at baseline (Clinical Dementia Rating score, 0). For mutation carriers, the annual rates of change for CSF tTau and pTau181 became significantly different from 0 approximately 10 years before the estimated year of onset (mean [SE] rates of change, 5.5 [2.8] for tTau [P =.05] and 0.7 [0.3] for pTau 181 [P =.04]) and 15 years before onset (mean [SE] rates of change, 5.4 [3.9] for tTau [P =.17] and 1.1 [0.5] for pTau181 [P =.03]), respectively. The rate of change of pTau181 was positive and increased at the early stages of the disease, showing a positive rate of change starting at 15 estimated years before onset until 5 estimated years before onset (mean [SE], 0.4 [0.3]), followed by a positive but decreasing rate of change at year 0 (mean [SE], 0.1 [0.3]) and then negative rates of change at 5 years (mean [SE], -0.3 [0.4]) and 10 years (mean [SE], -0.6 [0.6]) after symptom onset. In individuals without symptoms (Clinical Dementia Rating score, 0), the rates of change of CSF tTau and pTau181 were negatively associated with brain atrophy (high rates of change in CSF measures were associated with low rates of change in brain volume in asymptomatic stages). After symptom onset (Clinical Dementia Rating score, >0), an increased rate of brain atrophy was not associated with rates of change of levels of both CSF tTau and pTau181. Conclusions and Relevance: These findings suggest that CSF tTau and pTau181 may have different associations with brain atrophy across the disease time course. These results have implications for understanding the dynamics of disease pathobiology and interpreting neuronal injury biomarker concentrations in response to Alzheimer disease progression and disease-modifying therapies..
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Medical Association
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Tau
dc.subject
ALZHEIMER
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phospho tau
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CSF
dc.subject.classification
Neurología Clínica
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dc.subject.classification
Medicina Clínica
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dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
Association of Longitudinal Changes in Cerebrospinal Fluid Total Tau and Phosphorylated Tau 181 and Brain Atrophy with Disease Progression in Patients with Alzheimer Disease
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2022-07-25T15:32:09Z
dc.journal.volume
2
dc.journal.number
12
dc.journal.pagination
1-14
dc.journal.pais
Países Bajos
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dc.description.fil
Fil: Llibre Guerra, Jorge J.. Washington University in St. Louis; Estados Unidos
dc.description.fil
Fil: Li, Yan. Washington University in St. Louis; Estados Unidos
dc.description.fil
Fil: Schindler, Suzanne E.. Washington University in St. Louis; Estados Unidos
dc.description.fil
Fil: Gordon, Brian A.. Washington University in St. Louis; Estados Unidos
dc.description.fil
Fil: Fagan, Anne M.. Washington University in St. Louis; Estados Unidos
dc.description.fil
Fil: Morris, John C.. Washington University in St. Louis; Estados Unidos
dc.description.fil
Fil: Benzinger, Tammie L. S.. Washington University in St. Louis; Estados Unidos
dc.description.fil
Fil: Hassenstab, Jason. Washington University in St. Louis; Estados Unidos
dc.description.fil
Fil: Wang, Guoqiao. No especifíca;
dc.description.fil
Fil: Allegri, Ricardo Francisco. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
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Fil: Berman, Sarah B.. Washington University in St. Louis; Estados Unidos. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados Unidos
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Fil: Chhatwal, Jasmeer. Harvard Medical School; Estados Unidos
dc.description.fil
Fil: Farlow, Martin R.. Indiana University; Estados Unidos
dc.description.fil
Fil: Holtzman, David M.. Washington University in St. Louis; Estados Unidos
dc.description.fil
Fil: Jucker, Mathias. No especifíca;
dc.description.fil
Fil: Levin, Johannes. Ludwig Maximilians Universitat; Alemania
dc.description.fil
Fil: Noble, James M.. No especifíca;
dc.description.fil
Fil: Salloway, Stephen. University Brown; Estados Unidos
dc.description.fil
Fil: Schofield, Peter. University of New South Wales; Australia
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Fil: Karch, Celeste. Washington University in St. Louis; Estados Unidos
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Fil: Fox, Nick C.. Colegio Universitario de Londres; Reino Unido
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Fil: Xiong, Chengjie. Washington University in St. Louis; Estados Unidos
dc.description.fil
Fil: Bateman, Randall J.. Washington University in St. Louis; Estados Unidos
dc.description.fil
Fil: McDade, Eric. Washington University in St. Louis; Estados Unidos
dc.journal.title
JAMA Network Open
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1001/jamanetworkopen.2019.17126
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