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A beta and tau prio...
A beta and tau prion-like activities decline with longevity in the Alzheimer's disease human brain
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- Aoyagi, Atsushi (författare)
- Univ Calif San Francisco, UCSF Weill Inst Neurosci, Inst Neurodegenerat Dis, San Francisco, CA 94158 USA;Daiichi Sankyo Co Ltd, Tokyo 1408710, Japan
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- Condello, Carlo (författare)
- Karolinska Institutet
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- Stöhr, Jan (författare)
- Univ Calif San Francisco, UCSF Weill Inst Neurosci, Inst Neurodegenerat Dis, San Francisco, CA 94158 USA;Univ Calif San Francisco, UCSF Weill Inst Neurosci, Dept Neurol, San Francisco, CA 94158 USA;AC Immune SA, EPFL Innovat Pk,Bldg B, CH-1015 Lausanne, Switzerland
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- Yue, Weizhou (författare)
- Univ Calif San Francisco, UCSF Weill Inst Neurosci, Inst Neurodegenerat Dis, San Francisco, CA 94158 USA
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- Rivera, Brianna M. (författare)
- Univ Calif San Francisco, UCSF Weill Inst Neurosci, Inst Neurodegenerat Dis, San Francisco, CA 94158 USA
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- Lee, Joanne C. (författare)
- Univ Calif San Francisco, UCSF Weill Inst Neurosci, Inst Neurodegenerat Dis, San Francisco, CA 94158 USA
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- Woerman, Amanda L. (författare)
- Univ Calif San Francisco, UCSF Weill Inst Neurosci, Inst Neurodegenerat Dis, San Francisco, CA 94158 USA;Univ Calif San Francisco, UCSF Weill Inst Neurosci, Dept Neurol, San Francisco, CA 94158 USA
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- Halliday, Glenda (författare)
- Univ New South Wales, NeuRA, Sydney, NSW 2052, Australia;Univ New South Wales, Sch Med Sci, Sydney, NSW 2052, Australia;Univ Sydney, Brain & Mind Ctr, Sydney, NSW 2052, Australia
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- van Duinen, Sjoerd (författare)
- Leiden Univ, Med Ctr, Leiden, Netherlands
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- Ingelsson, Martin (författare)
- Uppsala universitet,Geriatrik
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- Lannfelt, Lars (författare)
- Uppsala universitet,Geriatrik
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- Graff, Caroline (författare)
- Karolinska Inst, Dept Neurobiol Care Sci & Soc, Solna, Sweden;Karolinska Univ Hosp, Unit Hereditary Dementias, Theme Aging, Solna, Sweden
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- Bird, Thomas D. (författare)
- Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA;Univ Washington, Dept Neurol, Seattle, WA 98195 USA
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- Keene, C. Dirk (författare)
- Univ Washington, Dept Neuropathol, Sch Med, Seattle, WA 98195 USA
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- Seeley, William W. (författare)
- Univ Calif San Francisco, UCSF Weill Inst Neurosci, Dept Neurol, San Francisco, CA 94158 USA;Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA
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- DeGrado, William F. (författare)
- Univ Calif San Francisco, UCSF Weill Inst Neurosci, Inst Neurodegenerat Dis, San Francisco, CA 94158 USA;Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA
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- Prusiner, Stanley B. (författare)
- Univ Calif San Francisco, UCSF Weill Inst Neurosci, Inst Neurodegenerat Dis, San Francisco, CA 94158 USA;Univ Calif San Francisco, UCSF Weill Inst Neurosci, Dept Neurol, San Francisco, CA 94158 USA;Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA
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(creator_code:org_t)
- AMER ASSOC ADVANCEMENT SCIENCE, 2019
- 2019
- Engelska.
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Ingår i: Science Translational Medicine. - : AMER ASSOC ADVANCEMENT SCIENCE. - 1946-6234 .- 1946-6242. ; 11:490
- Relaterad länk:
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https://europepmc.or...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- The hallmarks of Alzheimer's disease (AD) are the accumulation of A beta plaques and neurofibrillary tangles composed of hyperphosphorylated tau. We developed sensitive cellular assays using human embryonic kidney-293T cells to quantify intracellular self-propagating conformers of A beta in brain samples from patients with AD or other neurodegenerative diseases. Postmortem brain tissue from patients with AD had measurable amounts of pathological A beta conformers. Individuals over 80 years of age had the lowest amounts of prion-like A beta and phosphorylated tau. Unexpectedly, the longevity-dependent decrease in self-propagating tau conformers occurred in spite of increasing amounts of total insoluble tau. When corrected for the abundance of insoluble tau, the ability of postmortem AD brain homogenates to induce misfolded tau in the cellular assays showed an exponential decrease with longevity, with a half-life of about one decade over the age range of 37 to 99 years. Thus, our findings demonstrate an inverse correlation between longevity in patients with AD and the abundance of pathological tau conformers. Our cellular assays can be applied to patient selection for clinical studies and the development of new drugs and diagnostics for AD.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
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Aoyagi, Atsushi
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Condello, Carlo
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Stöhr, Jan
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Yue, Weizhou
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Rivera, Brianna ...
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Lee, Joanne C.
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visa fler...
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Woerman, Amanda ...
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Halliday, Glenda
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van Duinen, Sjoe ...
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Ingelsson, Marti ...
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Lannfelt, Lars
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Graff, Caroline
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Bird, Thomas D.
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Keene, C. Dirk
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Seeley, William ...
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DeGrado, William ...
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Prusiner, Stanle ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Neurovetenskaper
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Uppsala universitet
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Karolinska Institutet