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.
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We are grateful to Malika Farhed for excellent technical assistance, Julia Gerson for assistance with manuscript preparation and data analysis, and Lindsay Reese and Jennifer Deger for editorial assistance. We also thank Dr. Kelly T. Dineley and Dr. Yogesh Wairkar for their helpful suggestions. This work was supported by the Mitchell Center for Neurodegenerative Diseases and the Cullen Family Trust for Health Care .
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