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

Acta Neuropathologica Communications

Laura Vegas-Gomez,¹  Claudio Soto²  Rodrigo Morales²  Nelson Perez-Urrutia²  Claudia Duran-Aniotz²  Ines Moreno-Gonzalez²  Nazaret Gamez² 

[1] Department of Cell Biology, Faculty of Sciences, University of Malaga-IBIMA;Department of Neurology, The University of Texas Health Science Center at Houston;

关键词: Alzheimer’s disease;    Amyloid-beta;    Prions;    Strains;    Pathology;   

DOI  :  10.1186/s40478-021-01155-0

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown