Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Cryo-EM structures reveal tau filaments from Down syndrome adopt Alzheimer's disease fold.
Journal, issue, pages	Acta Neuropathol Commun, Vol. 12, Issue 1, Page 94, Year 2024
Publish date	Jun 12, 2024
Authors	Ujjayini Ghosh / Eric Tse / Hyunjun Yang / Marie Shi / Christoffer D Caro / Feng Wang / Gregory E Merz / Stanley B Prusiner / Daniel R Southworth / Carlo Condello /
PubMed Abstract	Down syndrome (DS) is a common genetic condition caused by trisomy of chromosome 21. Among their complex clinical features, including musculoskeletal, neurological, and cardiovascular disabilities, ...Down syndrome (DS) is a common genetic condition caused by trisomy of chromosome 21. Among their complex clinical features, including musculoskeletal, neurological, and cardiovascular disabilities, individuals with DS have an increased risk of developing progressive dementia and early-onset Alzheimer's disease (AD). This dementia is attributed to the increased gene dosage of the amyloid-β (Aβ) precursor protein gene, the formation of self-propagating Aβ and tau prion conformers, and the deposition of neurotoxic Aβ plaques and tau neurofibrillary tangles. Tau amyloid fibrils have previously been established to adopt many distinct conformations across different neurodegenerative conditions. Here, we report the characterization of brain samples from four DS cases spanning 36-63 years of age by spectral confocal imaging with conformation-specific dyes and cryo-electron microscopy (cryo-EM) to determine structures of isolated tau fibrils. High-resolution structures revealed paired helical filament (PHF) and straight filament (SF) conformations of tau that were identical to those determined from AD cases. The PHFs and SFs are made of two C-shaped protofilaments, each containing a cross-β/β-helix motif. Similar to filaments from AD cases, most filaments from the DS cases adopted the PHF form, while a minority (approximately 20%) formed SFs. Samples from the youngest individual with no documented dementia had sparse tau deposits. To isolate tau for cryo-EM from this challenging sample we used a novel affinity-grid method involving a graphene oxide surface derivatized with anti-tau antibodies. This method improved isolation and revealed that primarily tau PHFs and a minor population of chronic traumatic encephalopathy type II-like filaments were present in this youngest case. These findings expand the similarities between AD and DS to the molecular level, providing insight into their related pathologies and the potential for targeting common tau filament folds by small-molecule therapeutics and diagnostics.
External links	Acta Neuropathol Commun / PubMed:38867338 / PubMed Central
Methods	EM (helical sym.)
Resolution	2.7 - 3.2 Å
Structure data	45005 EMDB entry, No image 9bxi EMDB-45005, PDB-9bxi: Paired Helical Filament of tau amyloids found in Down Syndrome individuals Method: EM (helical sym.) / Resolution: 2.7 Å 45007 EMDB entry, No image 9bxo EMDB-45007, PDB-9bxo: Straight Filament of tau amyloids found in Down Syndrome individuals Method: EM (helical sym.) / Resolution: 3.0 Å 45008 EMDB entry, No image 9bxq EMDB-45008, PDB-9bxq: Paired Helical Filaments purified from Down Syndrome individual brain tissue applied to graphene oxide antibody affinity grids Method: EM (helical sym.) / Resolution: 3.1 Å 45009 EMDB entry, No image 9bxr EMDB-45009, PDB-9bxr: Straight Filaments purified from Down Syndrome individual brain tissue applied to graphene oxide antibody affinity grids Method: EM (helical sym.) / Resolution: 3.2 Å
Source	homo sapiens (human)
Keywords	PROTEIN FIBRIL / Amyloid / filament / neurodegeneration / Down syndrome