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TitleAlzheimer's disease seeded tau forms paired helical filaments yet lacks seeding potential.
Journal, issue, pagesJ Biol Chem, Vol. 300, Issue 9, Page 107730, Year 2024
Publish dateAug 28, 2024
AuthorsPu Duan / Aurelio J Dregni / Hong Xu / Lakshmi Changolkar / Virginia M-Y Lee / Edward B Lee / Mei Hong /
PubMed AbstractAlzheimer's disease (AD) and many other neurodegenerative diseases are characterized by pathological aggregation of the protein tau. These tau aggregates spread in a stereotypical spatiotemporal ...Alzheimer's disease (AD) and many other neurodegenerative diseases are characterized by pathological aggregation of the protein tau. These tau aggregates spread in a stereotypical spatiotemporal pattern in the brain of each disease, suggesting that the misfolded tau can recruit soluble monomers to adopt the same pathological structure. To investigate whether recruited tau indeed adopts the same structure and properties as the original seed, here we template recombinant full-length 0N3R tau, 0N4R tau, and an equimolar mixture of the two using sarkosyl-insoluble tau extracted from AD brain and determine the structures of the resulting fibrils using cryoelectron microscopy. We show that these cell-free amplified tau fibrils adopt the same molecular structure as the AD paired-helical filament (PHF) tau but are unable to template additional monomers. Therefore, the PHF structure alone is insufficient for defining the pathological properties of AD tau, and other biochemical components such as tau posttranslational modifications, other proteins, polyanionic cofactors, and salt are required for the prion-like serial propagation of tauopathies.
External linksJ Biol Chem / PubMed:39214304 / PubMed Central
MethodsEM (helical sym.)
Resolution2.69 - 2.97 Å
Structure data

45588

9cgx

EMDB-45588, PDB-9cgx:
Alzheimer's Disease Seeded 0N3R Tau Fibrils
Method: EM (helical sym.) / Resolution: 2.97 Å

45589

9cgz

EMDB-45589, PDB-9cgz:
Alzheimer's Disease Seeded Mixed 0N4R and 0N3R Tau Fibrils
Method: EM (helical sym.) / Resolution: 2.69 Å

Source
  • homo sapiens (human)
KeywordsPROTEIN FIBRIL / Tau / Amyloid / Cross-beta / Seeded-Fibril

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