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

Marcos J. Guerrero-Muñoz, Diana L. Castillo-Carranza, Shashirekha Krishnamurthy, Adriana A. Paulucci-Holthauzen, Urmi Sengupta, Cristian A. Lasagna-Reeves, Yembur Ahmad, George R. Jackson, Rakez Kayed

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)14-23
Number of pages10
JournalNeurobiology of Disease
Volume71
DOIs
StatePublished - Nov 2014

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Keywords

  • Alzheimer's disease
  • Aβ oligomers and cross seeding
  • Mixed proteinopathy
  • Protein aggregation

ASJC Scopus subject areas

  • Neurology

Cite this

Guerrero-Muñoz, M. J., Castillo-Carranza, D. L., Krishnamurthy, S., Paulucci-Holthauzen, A. A., Sengupta, U., Lasagna-Reeves, C. A., Ahmad, Y., Jackson, G. R., & Kayed, R. (2014). Amyloid-β oligomers as a template for secondary amyloidosis in Alzheimer's disease. Neurobiology of Disease, 71, 14-23. https://doi.org/10.1016/j.nbd.2014.08.008