info:eu-repo/semantics/article
A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer’s disease
Fecha
2020-03Registro en:
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
Autor
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
Resumen
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.