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

doi:10.1016/j.nbd.2014.08.008

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

Neurobiol Dis. 2014 Nov:71:14-23. doi: 10.1016/j.nbd.2014.08.008. Epub 2014 Aug 15.

Authors

Marcos J Guerrero-Muñoz¹, Diana L Castillo-Carranza¹, Shashirekha Krishnamurthy¹, Adriana A Paulucci-Holthauzen², Urmi Sengupta¹, Cristian A Lasagna-Reeves¹, Yembur Ahmad¹, George R Jackson³, Rakez Kayed⁴

Affiliations

¹ Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Neurology, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
² Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
³ Department of Neurology, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
⁴ Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Neurology, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA. Electronic address: rakayed@utmb.edu.

PMID: 25134727
DOI: 10.1016/j.nbd.2014.08.008

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.

Keywords: Alzheimer's disease; Aβ oligomers and cross seeding; Mixed proteinopathy; Protein aggregation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Alzheimer Disease / complications*
Alzheimer Disease / pathology*
Amyloid beta-Peptides / metabolism*
Animals
Cell Line, Tumor
Cerebral Amyloid Angiopathy / etiology*
DNA-Binding Proteins / metabolism*
Female
Frontal Lobe / metabolism*
Frontal Lobe / pathology
Humans
Imaging, Three-Dimensional
Male
Mice
Neuroblastoma / pathology
Neuroimaging
Peptide Fragments / metabolism*
Prions / metabolism
alpha-Synuclein / metabolism

Substances

Amyloid beta-Peptides
DNA-Binding Proteins
Peptide Fragments
Prions
alpha-Synuclein
amyloid beta-protein (1-42)

Supplementary concepts

Amyloid angiopathy