Tau filaments from multiple cases of sporadic and inherited Alzheimer's disease adopt a common fold.
Murzin, Alexey G
Garringer, Holly J
Springer Science and Business Media LLC
MetadataShow full item record
Falcon, B., Zhang, W., Schweighauser, M., Murzin, A. G., Vidal, R., Garringer, H. J., Ghetti, B., et al. (2018). Tau filaments from multiple cases of sporadic and inherited Alzheimer's disease adopt a common fold.. Acta Neuropathol, 136 (5), 699-708. https://doi.org/10.1007/s00401-018-1914-z
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.
Alzheimer’s disease, Electron cryo-microscopy, Immuno-gold negative-stain electron microscopy, Neurodegenerative diseases, Paired helical filaments, Straight filaments, Tau protein, Aged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Protein Precursor, Apolipoproteins E, Brain, Cryoelectron Microscopy, Female, Humans, Male, Microscopy, Immunoelectron, Middle Aged, Models, Anatomic, Mutation, Neurofibrillary Tangles, Exome Sequencing, tau Proteins
External DOI: https://doi.org/10.1007/s00401-018-1914-z
This record's URL: https://www.repository.cam.ac.uk/handle/1810/286006
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/
Recommended or similar items
The current recommendation prototype on the Apollo Repository will be turned off on 03 February 2023. Although the pilot has been fruitful for both parties, the service provider IKVA is focusing on horizon scanning products and so the recommender service can no longer be supported. We recognise the importance of recommender services in supporting research discovery and are evaluating offerings from other service providers. If you would like to offer feedback on this decision please contact us on: firstname.lastname@example.org
The following licence files are associated with this item: