Aggregate-Depleted Brain Fails to Induce Aβ Deposition in a Mouse Model of Alzheimer's Disease

Recent studies in animal models of Alzheimer's disease (AD) show that amyloid-beta (Aβ) misfolding can be transmissible; however, the mechanisms by which this process occurs have not been fully explored. The goal of this study was to analyze whether depletion of aggregates from an AD brain supp...

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Published inPloS one Vol. 9; no. 2; p. e89014
Main Authors Duran-Aniotz, Claudia, Morales, Rodrigo, Moreno-Gonzalez, Ines, Hu, Ping Ping, Fedynyshyn, Joseph, Soto, Claudio
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 12.02.2014
Public Library of Science (PLoS)
Subjects
Age
Aged, 80 and over
Aggregates
Aging
Alzheimer Disease - metabolism
Alzheimer's disease
Amyloid beta-Peptides - chemistry
Animal diseases
Animal models
Animals
Beads
Biology
Brain
Brain - drug effects
Brain - metabolism
Disease Models, Animal
Disease transmission
Humans
Male
Medical research
Medical schools
Medicine
Mice
Middle Aged
Neurodegenerative diseases
Neurology
Pathology
Peptidomimetics - pharmacology
Prions
Protein Aggregation, Pathological
Protein seeding
Proteins
Reagents
Rodents
Seeds
Transgenic animals
Online AccessGet full text
ISSN1932-6203
1932-6203
DOI10.1371/journal.pone.0089014

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Summary:Recent studies in animal models of Alzheimer's disease (AD) show that amyloid-beta (Aβ) misfolding can be transmissible; however, the mechanisms by which this process occurs have not been fully explored. The goal of this study was to analyze whether depletion of aggregates from an AD brain suppresses its in vivo "seeding" capability. Removal of aggregates was performed by using the Aggregate Specific Reagent 1 (ASR1) compound which has been previously described to specifically bind misfolded species. Our results show that pre-treatment with ASR1-coupled magnetic beads reduces the in vivo misfolding inducing capability of an AD brain extract. These findings shed light respect to the active principle responsible for the prion-like spreading of Alzheimer's amyloid pathology and open the possibility of using seeds-capturing reagents as a promising target for AD treatment.
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Conceived and designed the experiments: CD-A RM CS. Performed the experiments: CD-A RM IM-G PPH. Analyzed the data: CD-A RM IM-G CS. Contributed reagents/materials/analysis tools: JF. Wrote the paper: CD-A RM IM-G CS.
Competing Interests: This study was funded by a grant from Novartis Vaccines and Diagnostics, which owns the rights to commercialize the use of the ASR1 reagent. Dr. Soto served as Scientific Consultant for Novartis Vaccines and Diagnostics during the time in which the project was performed. Dr. Fedynyshyn was employed by the company during the first part of the work, but is no longer employed by Novartis. Dr. Fedynyshyn is an inventor on the patents related to the ASR-1 technology: Amyloid Beta Aggregates in Cerebro Spinal Fluid as Biomarker for Alzheimer's Disease. PCT/US2010/058450. There are no further patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0089014