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A beta 43 aggregate...
A beta 43 aggregates exhibit enhanced prion-like seeding activity in mice
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- Ruiz-Riquelme, Alejandro (author)
- Univ Toronto, Canada; UCL, England
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- Mao, Alison (author)
- Univ Toronto, Canada; Univ Toronto, Canada
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- Barghash, Marim M. (author)
- Univ Toronto, Canada; Univ Toronto, Canada
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- Lau, Heather H. C. (author)
- Univ Toronto, Canada; Univ Toronto, Canada
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- Stuart, Erica (author)
- Univ Toronto, Canada
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- Kovacs, Gabor G. (author)
- Univ Toronto, Canada; Univ Toronto, Canada; Univ Hlth Network, Canada; Univ Hlth Network, Canada
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- Nilsson, Peter (author)
- Linköpings universitet,Kemi,Tekniska fakulteten
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- Fraser, Paul E. (author)
- Univ Toronto, Canada; Univ Toronto, Canada
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- Schmitt-Ulms, Gerold (author)
- Univ Toronto, Canada; Univ Toronto, Canada
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- Watts, Joel C. (author)
- Univ Toronto, Canada; Univ Toronto, Canada
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(creator_code:org_t)
- 2021-05-10
- 2021
- English.
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In: Acta neuropathologica communications. - : BMC. - 2051-5960. ; 9:1
- Related links:
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https://liu.diva-por... (primary) (Raw object)
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https://actaneurocom...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- When injected into genetically modified mice, aggregates of the amyloid-beta (A beta) peptide from the brains of Alzheimers disease (AD) patients or transgenic AD mouse models seed cerebral A beta deposition in a prion-like fashion. Within the brain, A beta exists as a pool of distinct C-terminal variants with lengths ranging from 37 to 43 amino acids, yet the relative contribution of individual C-terminal A beta variants to the seeding behavior of A beta aggregates remains unknown. Here, we have investigated the relative seeding activities of A beta aggregates composed exclusively of recombinant A beta 38, A beta 40, A beta 42, or A beta 43. Cerebral A beta 42 levels were not increased in App(NL-F) knock-in mice injected with A beta 38 or A beta 40 aggregates and were only increased in a subset of mice injected with A beta 42 aggregates. In contrast, significant accumulation of A beta 42 was observed in the brains of all mice inoculated with A beta 43 aggregates, and the extent of A beta 42 induction was comparable to that in mice injected with brain-derived A beta seeds. Mice inoculated with A beta 43 aggregates exhibited a distinct pattern of cerebral A beta pathology compared to mice injected with brain-derived A beta aggregates, suggesting that recombinant A beta 43 may polymerize into a unique strain. Our results indicate that aggregates containing longer A beta C-terminal variants are more potent inducers of cerebral A beta deposition and highlight the potential role of A beta 43 seeds as a crucial factor in the initial stages of A beta pathology in AD.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Alzheimers disease; Prion-like propagation; Amyloid-beta; Knock-in mice; Strains
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Ruiz-Riquelme, A ...
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Mao, Alison
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Barghash, Marim ...
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Lau, Heather H. ...
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Stuart, Erica
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Kovacs, Gabor G.
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show more...
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Nilsson, Peter
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Fraser, Paul E.
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Schmitt-Ulms, Ge ...
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Watts, Joel C.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Acta neuropathol ...
- By the university
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Linköping University