Endo-lysosomal Aβ concentration and pH trigger formation of Aβ oligomers that potently induce Tau missorting
Aβ oligomers (AβO) are thought to represent the main toxic species in Alzheimer’s disease but very high Aβ concentrations are required to study them in vitro and it remains unknown what role these off-pathway oligomers play in vivo. Here, the authors use a dimeric variant of Aβ termed dimAβ, where t...
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Nature Portfolio
2021
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oai:doaj.org-article:b6f61d39315341c6800e49fcfe3a5b642021-12-02T18:47:00ZEndo-lysosomal Aβ concentration and pH trigger formation of Aβ oligomers that potently induce Tau missorting10.1038/s41467-021-24900-42041-1723https://doaj.org/article/b6f61d39315341c6800e49fcfe3a5b642021-07-01T00:00:00Zhttps://doi.org/10.1038/s41467-021-24900-4https://doaj.org/toc/2041-1723Aβ oligomers (AβO) are thought to represent the main toxic species in Alzheimer’s disease but very high Aβ concentrations are required to study them in vitro and it remains unknown what role these off-pathway oligomers play in vivo. Here, the authors use a dimeric variant of Aβ termed dimAβ, where two Aβ40 units are linked, which facilitates to study AβO formation kinetics and they observe that Aβ off-pathway oligomer formation is strongly accelerated at endo-lysosomal pH, while amyloid fibril formation is delayed. Furthermore, the authors demonstrate that dimAβ is a disease-relevant model construct for pathogenic AβO formation by showing that dimAβ AβOs target dendritic spines and induce AD-like somatodendritic Tau missorting.Marie P. SchützmannFilip HaseckeSarah BachmannMara ZielinskiSebastian HänschGunnar F. SchröderHans ZempelWolfgang HoyerNature PortfolioarticleScienceQENNature Communications, Vol 12, Iss 1, Pp 1-14 (2021) |
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Science Q |
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Science Q Marie P. Schützmann Filip Hasecke Sarah Bachmann Mara Zielinski Sebastian Hänsch Gunnar F. Schröder Hans Zempel Wolfgang Hoyer Endo-lysosomal Aβ concentration and pH trigger formation of Aβ oligomers that potently induce Tau missorting |
| description |
Aβ oligomers (AβO) are thought to represent the main toxic species in Alzheimer’s disease but very high Aβ concentrations are required to study them in vitro and it remains unknown what role these off-pathway oligomers play in vivo. Here, the authors use a dimeric variant of Aβ termed dimAβ, where two Aβ40 units are linked, which facilitates to study AβO formation kinetics and they observe that Aβ off-pathway oligomer formation is strongly accelerated at endo-lysosomal pH, while amyloid fibril formation is delayed. Furthermore, the authors demonstrate that dimAβ is a disease-relevant model construct for pathogenic AβO formation by showing that dimAβ AβOs target dendritic spines and induce AD-like somatodendritic Tau missorting. |
| format |
article |
| author |
Marie P. Schützmann Filip Hasecke Sarah Bachmann Mara Zielinski Sebastian Hänsch Gunnar F. Schröder Hans Zempel Wolfgang Hoyer |
| author_facet |
Marie P. Schützmann Filip Hasecke Sarah Bachmann Mara Zielinski Sebastian Hänsch Gunnar F. Schröder Hans Zempel Wolfgang Hoyer |
| author_sort |
Marie P. Schützmann |
| title |
Endo-lysosomal Aβ concentration and pH trigger formation of Aβ oligomers that potently induce Tau missorting |
| title_short |
Endo-lysosomal Aβ concentration and pH trigger formation of Aβ oligomers that potently induce Tau missorting |
| title_full |
Endo-lysosomal Aβ concentration and pH trigger formation of Aβ oligomers that potently induce Tau missorting |
| title_fullStr |
Endo-lysosomal Aβ concentration and pH trigger formation of Aβ oligomers that potently induce Tau missorting |
| title_full_unstemmed |
Endo-lysosomal Aβ concentration and pH trigger formation of Aβ oligomers that potently induce Tau missorting |
| title_sort |
endo-lysosomal aβ concentration and ph trigger formation of aβ oligomers that potently induce tau missorting |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/b6f61d39315341c6800e49fcfe3a5b64 |
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