Amyloid pathology arrangements in Alzheimer's disease brains modulate in vivo seeding capability

Amyloid-β (Aβ) misfolding is one of the hallmark pathological features of Alzheimer's disease (AD). AD can manifest with diverse symptomatology including variable rates of cognitive decline, duration of clinical disease, and other detrimental changes. Several reports suggest that conformational...

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Detalles Bibliográficos
Autores: Duran-Aniotz, Claudia, Moreno-Gonzalez, Ines, Gamez, Nazaret, Perez-Urrutia, Nelson, Vegas-Gomez, Laura, Soto, Claudio, Morales, Rodrigo
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/18299
Acceso en línea:http://hdl.handle.net/20.500.12105/18299
Access Level:acceso abierto
Palabra clave:Alzheimer’s disease
Amyloid-beta
Pathology
Prions
Strains
Enfermedad de alzheimer
beta-Amiloides
Patología
Priones
Aged
Descripción
Sumario:Amyloid-β (Aβ) misfolding is one of the hallmark pathological features of Alzheimer's disease (AD). AD can manifest with diverse symptomatology including variable rates of cognitive decline, duration of clinical disease, and other detrimental changes. Several reports suggest that conformational diversity in misfolded Aβ is a leading factor for clinical variability in AD, analogous to what it has been described for prion strains in prion diseases. Notably, prion strains generate diverse patterns of misfolded protein deposition in the brains of affected individuals. Here, we tested the in vivo prion-like transmission features of four AD brains displaying particular patterns of amyloidosis. AD brains induced different phenotypes in recipient mice, as evaluated by their specific seeding activity, as well as the total amount of Aβ deposited surrounding vascular structures and the reactivity of amyloid pathology to thioflavin S. Our results support the notion that AD-subtypes are encoded in disease-associated Aβ. Further research exploring whether AD include a spectrum of different clinical conditions or syndromes may pave the way to personalized diagnosis and treatments.