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

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.