33WP
Single protofilament with the Alzheimer tau fold and the V337M mutation from seeded primary murine neurons
Summary for 33WP
| Entry DOI | 10.2210/pdb33wp/pdb |
| EMDB information | 59642 |
| Descriptor | Isoform Fetal-tau of Microtubule-associated protein tau (1 entity in total) |
| Functional Keywords | tau, alzheimer fold, protein fibril |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 3 |
| Total formula weight | 110559.55 |
| Authors | |
| Primary citation | Huang, M.,Lovestam, S.,Cheam, K.A.X.,Ghetti, B.,McEwan, W.A.,Scheres, S.H.W.,Goedert, M. Templated paired helical filament formation and tau fold-dependent inclusion morphologies in primary neurons. Biorxiv, 2026 Cited by PubMed Abstract: Neurodegenerative tauopathies are characterized by the abnormal assembly of tau into amyloid filaments with distinct, disease-specific folds. These filaments are proposed to spread in a prion-like manner, thus underlying the progression of pathology in diseased brains. A prediction of this hypothesis is that tau filaments will induce progeny filaments identical to the input seed material, yet cellular models of templated tau assembly have failed to fully recapitulate brain-derived filament structures. Here, we show that mixed primary mouse cortical neurons overexpressing full-length human tau via adeno-associated virus transduction propagate Alzheimer's disease paired helical filaments upon exposure to human brain-derived seeds. Using minimal tags and core mutations, we were able to unambiguously differentiate induced aggregates from the original seeds. Super-resolution microscopy and live-cell imaging revealed progressive inclusion formation in neurons. Moreover, seeding primary neurons with brain extracts from individuals with Pick's disease, corticobasal degeneration and progressive supranuclear palsy induced the formation of morphologically distinct inclusions. Together, these findings establish that primary neurons provide an environment for the faithful propagation of paired helical filaments and show that tau filament folds dictate higher-order inclusion morphologies within neurons. PubMed: 42926395DOI: 10.64898/2026.09.30.755038 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.9 Å) |
Structure validation
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