title: Amyloid-β oligomers as a template for secondary amyloidosis in Alzheimer's disease.
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.
authors.affiliation: 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.
authors.forename: Marcos J
authors.initials: MJ
authors.lastname: Guerrero-Muñoz
authors.affiliation: 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.
authors.forename: Diana L
authors.initials: DL
authors.lastname: Castillo-Carranza
authors.affiliation: 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.
authors.forename: Shashirekha
authors.initials: S
authors.lastname: Krishnamurthy
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Adriana A
authors.initials: AA
authors.lastname: Paulucci-Holthauzen
authors.affiliation: 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.
authors.forename: Urmi
authors.initials: U
authors.lastname: Sengupta
authors.affiliation: 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.
authors.forename: Cristian A
authors.initials: CA
authors.lastname: Lasagna-Reeves
authors.affiliation: 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.
authors.forename: Yembur
authors.initials: Y
authors.lastname: Ahmad
authors.affiliation: 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.
authors.forename: George R
authors.initials: GR
authors.lastname: Jackson
authors.affiliation: 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.
authors.forename: Rakez
authors.initials: R
authors.lastname: Kayed
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D016657:Cerebral Amyloid Angiopathy / Q000209:etiology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D021621:Imaging, Three-Dimensional; D008297:Male; D051379:Mice; D009447:Neuroblastoma / Q000473:pathology; D059906:Neuroimaging; D010446:Peptide Fragments / Q000378:metabolism*; D011328:Prions / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D004268:DNA-Binding Proteins; D010446:Peptide Fragments; D011328:Prions; D051844:alpha-Synuclein; C075222:amyloid beta-protein (1-42)
keywords: Alzheimer's disease; Aβ oligomers and cross seeding; Mixed proteinopathy; Protein aggregation