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Amyloid-beta oligomers as a template for secondary amyloidosis in;Alzheimer's disease
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Guerrero-Munoz, Marcos J.;Castillo-Carranza, Diana L.;Krishnamurthy, Shashirekha;Paulucci-Holthauzen, Adriana A.;Sengupta, Urmi;Lasagna-Reeves, Cristian A.;Ahmad, Yembur;Jackson, George R.;Kayed, Rakez
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[Guerrero-Munoz, Marcos J.; Castillo-Carranza, Diana L.; Krishnamurthy, Shashirekha; Sengupta, Urmi; Lasagna-Reeves, Cristian A.; Ahmad, Yembur; Kayed, Rakez] Univ Texas Med Branch, Mitchell Ctr Neurodegenerat Dis, Galveston, TX 77555 USA.;[Guerrero-Munoz, Marcos J.; Castillo-Carranza, Diana L.; Krishnamurthy, Shashirekha; Sengupta, Urmi; Lasagna-Reeves, Cristian A.; Ahmad, Yembur; Jackson, George R.; Kayed, Rakez] Univ Texas Med Branch, Dept Neurol, Galveston, TX 77555 USA.;[Guerrero-Munoz, Marcos J.; Castillo-Carranza, Diana L.; Krishnamurthy, Shashirekha; Sengupta, Urmi; Lasagna-Reeves, Cristian A.; Ahmad, Yembur; Jackson, George R.; Kayed, Rakez] Univ Texas Med Branch, Dept Neurosci & Cell Biol, Galveston, TX 77555 USA.;[Paulucci-Holthauzen, Adriana A.] Univ Texas Med Branch, Dept Biochem & Mol Biol, Galveston, TX 77555 USA.
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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-beta, prion protein, alpha-synuclein, and TDP-43 phosphorylated at serines 409 and 410. These data and in vitro results suggest that A beta 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-beta therapy has been unsuccessful. (C) 2014 Elsevier Inc. All rights reserved. |
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Keywords:
COGNITIVE DECLINE
PARKINSONS-DISEASE
PASSIVE-IMMUNIZATION
FIBRIL FORMATION
LEWY BODIES
A-BETA
ALPHA-SYNUCLEIN
MICE
APP TRANSGENIC
CELLULAR PRION PROTEIN
AMYOTROPHIC-LATERAL-SCLEROSIS
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