Tau filaments from multiple cases of sporadic and inherited Alzheimer’s disease adopt a common fold

Clicks: 177
ID: 118272
2018
Free PDF
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal
Emerging

Ranked #208 of 438 articles by views in acta neuropathologica

Most read Least read

Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 438 in total.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
The ordered assembly of tau protein into abnormal filaments is a defining characteristic of Alzheimer’s disease (AD) and other neurodegenerative disorders. It is not known if the structures of tau filaments vary within, or between, the brains of individuals with AD. We used a combination of electron cryo-microscopy (cryo-EM) and immuno-gold negative-stain electron microscopy (immuno-EM) to determine the structures of paired helical filaments (PHFs) and straight filaments (SFs) from the frontal cortex of 17 cases of AD (15 sporadic and 2 inherited) and 2 cases of atypical AD (posterior cortical atrophy). The high-resolution structures of PHFs and SFs from the frontal cortex of 3 cases of AD, 2 sporadic and 1 inherited, were determined by cryo-EM. We also used immuno-EM to study the PHFs and SFs from a number of cortical and subcortical brain regions. PHFs outnumbered SFs in all AD cases. By cryo-EM, PHFs and SFs were made of two C-shaped protofilaments with a combined cross-β/β-helix structure, as described previously for one case of AD. The higher resolution structures obtained here showed two additional amino acids at each end of the protofilament. The immuno-EM findings, which indicated the presence of repeats 3 and 4, but not of the N-terminal regions of repeats 1 and 2, of tau in the filament cores of all AD cases, were consistent with the cryo-EM results. These findings show that there is no significant variation in tau filament structures between individuals with AD. This knowledge will be crucial for understanding the mechanisms that underlie tau filament formation and for developing novel diagnostics and therapies.
Reference Key
falcon2018actatau Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Benjamin Falcon;Wenjuan Zhang;Manuel Schweighauser;Alexey G. Murzin;Ruben Vidal;Holly J. Garringer;Bernardino Ghetti;Sjors H. W. Scheres;Michel Goedert;Benjamin Falcon;Wenjuan Zhang;Manuel Schweighauser;Alexey G. Murzin;Ruben Vidal;Holly J. Garringer;Bernardino Ghetti;Sjors H. W. Scheres;Michel Goedert;
Journal acta neuropathologica
Year 2018
DOI
doi:10.1007/s00401-018-1914-z
URL
https://link.springer.com/article/10.1007/s00401-018-1914-z
Keywords
pathology neurosciences

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.