Unique pathological tau conformers from Alzheimer's brains transmit tau pathology in nontransgenic mice.
J Exp Med
; 213(12): 2635-2654, 2016 11 14.
Article
en En
| MEDLINE
| ID: mdl-27810929
ABSTRACT
Filamentous tau aggregates are hallmark lesions in numerous neurodegenerative diseases, including Alzheimer's disease (AD). Cell culture and animal studies showed that tau fibrils can undergo cell-to-cell transmission and seed aggregation of soluble tau, but this phenomenon was only robustly demonstrated in models overexpressing tau. In this study, we found that intracerebral inoculation of tau fibrils purified from AD brains (AD-tau), but not synthetic tau fibrils, resulted in the formation of abundant tau inclusions in anatomically connected brain regions in nontransgenic mice. Recombinant human tau seeded by AD-tau revealed unique conformational features that are distinct from synthetic tau fibrils, which could underlie the differential potency in seeding physiological levels of tau to aggregate. Therefore, our study establishes a mouse model of sporadic tauopathies and points to important differences between tau fibrils that are generated artificially and authentic ones that develop in AD brains.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Encéfalo
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Proteínas tau
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Tauopatías
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Enfermedad de Alzheimer
Límite:
Animals
Idioma:
En
Revista:
J Exp Med
Año:
2016
Tipo del documento:
Article