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

N.R. Barthélemy; Y. Li; N. Joseph-Mathurin; B.A. Gordon; J. Hassenstab; T.L.S. Benzinger; V. Buckles; A.M. Fagan; R.J. Perrin; A.M. Goate; J.C. Morris; C.M. Karch; C. Xiong; R. Allegri; P.C. Mendez; S.B. Berman; T. Ikeuchi; H. Mori; H. Shimada; M. Shoji; K. Suzuki; J. Noble; M. Farlow; J. Chhatwal; N.R. Graff-Radford; S. Salloway; P.R. Schofield; C.L. Masters; R.N. Martins; A. O’Connor; N.C. Fox; J. Levin; M. Jucker; A. Gabelle; S. Lehmann; C. Sato; R.J. Bateman; E. McDade; R. Bateman; J. Bechara; T. Benzinger; S. Berman; C. Bodge; S. Brandon; W. Brooks; J. Buck; S. Chea; P. Chrem Mendez; H. Chui; J. Cinco; J. Clifford; C. Cruchaga; T. Donahue; J. Douglas; N. Edigo; N. Erekin-Taner; A. Fagan; C. Fitzpatrick; G. Flynn; N. Fox; E. Franklin; H. Fujii; C. Gant; S. Gardener; B. Ghetti; A. Goate; J. Goldman; B. Gordon; N. Graff-Radford; J. Gray; A. Groves; L. Hoechst-Swisher; D. Holtzman; R. Hornbeck; S. Houeland DiBari; S. Ikonomovic; G. Jerome; C. Karch; K. Kasuga; T. Kawarabayashi; W. Klunk; R. Koeppe; E. Kuder-Buletta; C. Laske; J-H Lee; R. Martins; N.S. Mason; C. Masters; D. Maue-Dreyfus; J. Morris; A. Nagamatsu; K. Neimeyer; J. Norton; R. Perrin; M. Raichle; A. Renton; J. Ringman; J.H. Roh; P. Schofield; W. Sigurdson; H. Sohrabi; P. Sparks; K. Taddei; P. Wang; X. Xu

doi:10.1038/s41591-020-0781-z

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

Journal article

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

N.R. Barthélemy, Y. Li, N. Joseph-Mathurin, B.A. Gordon, J. Hassenstab, T.L.S. Benzinger, V. Buckles, A.M. Fagan, R.J. Perrin, A.M. Goate, …

Nature Medicine, Vol.26(3), pp.398-407

2020

DOI: https://doi.org/10.1038/s41591-020-0781-z

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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.

Details

Title: A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer’s disease
Authors/Creators: N.R. Barthélemy (Author/Creator) - Washington University in St. Louis
Y. Li (Author/Creator) - Washington University in St. Louis
N. Joseph-Mathurin (Author/Creator) - Washington University in St. Louis
B.A. Gordon (Author/Creator) - Washington University in St. Louis
J. Hassenstab (Author/Creator) - Washington University in St. Louis
T.L.S. Benzinger (Author/Creator) - Washington University in St. Louis
V. Buckles (Author/Creator) - Washington University in St. Louis
A.M. Fagan (Author/Creator) - Washington University in St. Louis
R.J. Perrin (Author/Creator) - Washington University in St. Louis
A.M. Goate (Author/Creator) - Icahn School of Medicine at Mount Sinai
J.C. Morris (Author/Creator) - Washington University in St. Louis
C.M. Karch (Author/Creator) - Washington University in St. Louis
C. Xiong (Author/Creator) - Washington University in St. Louis
R. Allegri (Author/Creator) - Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia
P.C. Mendez (Author/Creator) - Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia
S.B. Berman (Author/Creator) - University of Pittsburgh
T. Ikeuchi (Author/Creator) - Niigata University
H. Mori (Author/Creator) - Osaka City University
H. Shimada (Author/Creator) - Osaka City University
M. Shoji (Author/Creator) - Hirosaki University
K. Suzuki (Author/Creator) - The University of Tokyo
J. Noble (Author/Creator) - Columbia University
M. Farlow (Author/Creator) - Indiana University – Purdue University Indianapolis
J. Chhatwal (Author/Creator) - Massachusetts General Hospital
N.R. Graff-Radford (Author/Creator) - Jacksonville College
S. Salloway (Author/Creator) - Brown University
P.R. Schofield (Author/Creator) - Neuroscience Research Australia
C.L. Masters (Author/Creator) - Florey Institute of Neuroscience and Mental Health
R.N. Martins (Author/Creator) - Edith Cowan University
A. O’Connor (Author/Creator)
N.C. Fox (Author/Creator) - UK Dementia Research Institute
J. Levin (Author/Creator) - German Center for Neurodegenerative Diseases
M. Jucker (Author/Creator) - German Center for Neurodegenerative Diseases
A. Gabelle (Author/Creator) - Inserm
S. Lehmann (Author/Creator) - Inserm
C. Sato (Author/Creator) - Washington University in St. Louis
R.J. Bateman (Author/Creator) - Washington University in St. Louis
E. McDade (Author/Creator) - Washington University in St. Louis
R. Allegri (Author/Creator) - Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia
R. Bateman (Author/Creator) - Washington University in St. Louis
J. Bechara (Author/Creator)
T. Benzinger (Author/Creator)
S. Berman (Author/Creator) - University of Pittsburgh
C. Bodge (Author/Creator)
S. Brandon (Author/Creator)
W. Brooks (Author/Creator)
J. Buck (Author/Creator)
V. Buckles (Author/Creator) - Washington University in St. Louis
S. Chea (Author/Creator)
J. Chhatwal (Author/Creator) - Massachusetts General Hospital
P. Chrem Mendez (Author/Creator)
H. Chui (Author/Creator)
J. Cinco (Author/Creator)
J. Clifford (Author/Creator)
C. Cruchaga (Author/Creator)
T. Donahue (Author/Creator)
J. Douglas (Author/Creator)
N. Edigo (Author/Creator)
N. Erekin-Taner (Author/Creator)
A. Fagan (Author/Creator) - Washington University in St. Louis
M. Farlow (Author/Creator) - Indiana University – Purdue University Indianapolis
C. Fitzpatrick (Author/Creator)
G. Flynn (Author/Creator)
N. Fox (Author/Creator) - UK Dementia Research Institute
E. Franklin (Author/Creator)
H. Fujii (Author/Creator)
C. Gant (Author/Creator)
S. Gardener (Author/Creator)
B. Ghetti (Author/Creator)
A. Goate (Author/Creator) - Icahn School of Medicine at Mount Sinai
J. Goldman (Author/Creator)
B. Gordon (Author/Creator) - Washington University in St. Louis
N. Graff-Radford (Author/Creator) - Jacksonville College
J. Gray (Author/Creator)
A. Groves (Author/Creator)
J. Hassenstab (Author/Creator) - Washington University in St. Louis
L. Hoechst-Swisher (Author/Creator)
D. Holtzman (Author/Creator)
R. Hornbeck (Author/Creator)
S. Houeland DiBari (Author/Creator)
T. Ikeuchi (Author/Creator) - Niigata University
S. Ikonomovic (Author/Creator)
G. Jerome (Author/Creator)
M. Jucker (Author/Creator) - German Center for Neurodegenerative Diseases
C. Karch (Author/Creator) - Washington University in St. Louis
K. Kasuga (Author/Creator)
T. Kawarabayashi (Author/Creator)
W. Klunk (Author/Creator)
R. Koeppe (Author/Creator)
E. Kuder-Buletta (Author/Creator)
C. Laske (Author/Creator)
J-H Lee (Author/Creator)
J. Levin (Author/Creator) - German Center for Neurodegenerative Diseases
R. Martins (Author/Creator) - Edith Cowan University
N.S. Mason (Author/Creator)
C. Masters (Author/Creator) - Florey Institute of Neuroscience and Mental Health
D. Maue-Dreyfus (Author/Creator)
E. McDade (Author/Creator) - Washington University in St. Louis
H. Mori (Author/Creator) - Osaka City University
J. Morris (Author/Creator) - Washington University in St. Louis
A. Nagamatsu (Author/Creator)
K. Neimeyer (Author/Creator)
J. Noble (Author/Creator) - Columbia University
J. Norton (Author/Creator)
R. Perrin (Author/Creator) - Washington University in St. Louis
M. Raichle (Author/Creator)
A. Renton (Author/Creator)
J. Ringman (Author/Creator)
J.H. Roh (Author/Creator)
S. Salloway (Author/Creator) - Brown University
P. Schofield (Author/Creator) - Neuroscience Research Australia
H. Shimada (Author/Creator) - Osaka City University
W. Sigurdson (Author/Creator)
H. Sohrabi (Author/Creator)
P. Sparks (Author/Creator)
K. Suzuki (Author/Creator) - The University of Tokyo
K. Taddei (Author/Creator)
P. Wang (Author/Creator)
C. Xiong (Author/Creator) - Washington University in St. Louis
X. Xu (Author/Creator)
Publication Details: Nature Medicine, Vol.26(3), pp.398-407
Publisher: Nature Research
Identifiers: 991005542693307891
Murdoch Affiliation: Murdoch University
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.52 Neurodegenerative Diseases; 1.52.60 Dementia
Web Of Science research areas: Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental
ESI research areas: Molecular Biology & Genetics