A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer's disease
Author
Barthelemy, NR; Li, Y; Joseph-Mathurin, N; Gordon, BA; Hassenstab, J; Benzinger, TLS; Buckles, V; Fagan, AM; Perrin, RJ; Goate, AM; ...Date
2020-03-01Source Title
Nature MedicinePublisher
NATURE RESEARCHUniversity of Melbourne Author/s
Masters, ColinAffiliation
Florey Department of Neuroscience and Mental HealthMetadata
Show full item recordDocument Type
Journal ArticleCitations
Barthelemy, N. R., Li, Y., Joseph-Mathurin, N., Gordon, B. A., Hassenstab, J., Benzinger, T. L. S., Buckles, V., Fagan, A. M., Perrin, R. J., Goate, A. M., Morris, J. C., Karch, C. M., Xiong, C., Allegri, R., Mendez, P. C., Berman, S. B., Ikeuchi, T., Mori, H., Shimada, H. ,... Xu, X. (2020). A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer's disease. NATURE MEDICINE, 26 (3), pp.398-+. https://doi.org/10.1038/s41591-020-0781-z.Access Status
Access this item via the Open Access locationOpen Access URL
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309367Abstract
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.
Export Reference in RIS Format
Endnote
- Click on "Export Reference in RIS Format" and choose "open with... Endnote".
Refworks
- Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References