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Serial propagation ...
Serial propagation of distinct strains of A beta prions from Alzheimer's disease patients
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Watts, Joel C. (författare)
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Condello, Carlo (författare)
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Stoehr, Jan (författare)
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Oehler, Abby (författare)
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Lee, Joanne (författare)
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DeArmond, Stephen J. (författare)
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- Lannfelt, Lars (författare)
- Uppsala universitet,Geriatrik
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- Ingelsson, Martin (författare)
- Uppsala universitet,Geriatrik
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Giles, Kurt (författare)
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Prusiner, Stanley B. (författare)
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(creator_code:org_t)
- 2014-06-30
- 2014
- Engelska.
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 111:28, s. 10323-10328
- Relaterad länk:
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https://www.pnas.org...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- An increasing number of studies argues that self-propagating protein conformations (i.e., prions) feature in the pathogenesis of several common neurodegenerative diseases. Mounting evidence contends that aggregates of the amyloid-beta (A beta) peptide become self-propagating in Alzheimer's disease (AD) patients. An important characteristic of prions is their ability to replicate distinct strains, the biological information for which is enciphered within different conformations of protein aggregates. To investigate whether distinct strains of A beta prions can be discerned in AD patients, we performed transmission studies in susceptible transgenic mice using brain homogenates from sporadic or heritable (Arctic and Swedish) AD cases. Mice inoculated with the Arctic AD sample exhibited a pathology that could be distinguished from mice inoculated with the Swedish or sporadic AD samples, which was judged by differential accumulation of A beta isoforms and the morphology of cerebrovascular A beta deposition. Unlike Swedish AD- or sporadic AD-inoculated animals, Arctic AD-inoculated mice, like Arctic AD patients, displayed a prominent A beta 38-containing cerebral amyloid angiopathy. The divergent transmission behavior of the Arctic AD sample compared with the Swedish and sporadic AD samples was maintained during second passage in mice, showing that A beta strains are serially transmissible. We conclude that at least two distinct strains of A beta prions can be discerned in the brains of AD patients and that strain fidelity was preserved on serial passage in mice. Our results provide a potential explanation for the clinical and pathological heterogeneity observed in AD patients.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Geriatrik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Geriatrics (hsv//eng)
Nyckelord
- neurodegeneration
- bioluminescence imaging
- seeding
- proteinopathies
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- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
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Watts, Joel C.
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Condello, Carlo
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Stoehr, Jan
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Oehler, Abby
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Lee, Joanne
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DeArmond, Stephe ...
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visa fler...
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Lannfelt, Lars
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Ingelsson, Marti ...
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Giles, Kurt
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Prusiner, Stanle ...
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Geriatrik
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Uppsala universitet