Amyloid-β oligomers as a template for secondary amyloidosis in Alzheimer's disease

Neurobiology of Disease

Diana L. Castillo-Carranza¹  Urmi Sengupta¹  George R. Jackson¹  Shashirekha Krishnamurthy²  Rakez Kayed²  Cristian A. Lasagna-Reeves²  Marcos J. Guerrero-Muñoz³  Yembur Ahmad³  Adriana A. Paulucci-Holthauzen³ 

[1]Department of Neurology, University of Texas Medical Branch, Galveston, TX 77555, USA

[2]Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA

[3]Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA

关键词: Protein aggregation;    Alzheimer's disease;    Mixed proteinopathy;    Aβ oligomers and cross seeding;   

DOI  :  

来源: DOAJ

【 摘 要 】

Alzheimer's disease is a complex disease characterized by overlapping phenotypes with different neurodegenerative disorders. Oligomers are considered the most toxic species in amyloid pathologies. We examined human AD brain samples using an anti-oligomer antibody generated in our laboratory and detected potential hybrid oligomers composed of amyloid-β, prion protein, α-synuclein, and TDP-43 phosphorylated at serines 409 and 410. These data and in vitro results suggest that Aβ oligomer seeds act as a template for the aggregation of other proteins and generate an overlapping phenotype with other neuronal disorders. Furthermore, these results could explain why anti-amyloid-β therapy has been unsuccessful.

【 授权许可】

Unknown