TY - JOUR
T1 - Aggregate-depleted brain fails to induce Aβ deposition in a mouse model of Alzheimer's disease
AU - Duran-Aniotz, Claudia
AU - Morales, Rodrigo
AU - Moreno-Gonzalez, Ines
AU - Hu, Ping Ping
AU - Fedynyshyn, Joseph
AU - Soto, Claudio
N1 - Funding Information:
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.
PY - 2014/2/12
Y1 - 2014/2/12
N2 - Recent studies in animal models of Alzheimer's disease (AD) show that amyloid-beta (Ab) 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.
AB - Recent studies in animal models of Alzheimer's disease (AD) show that amyloid-beta (Ab) 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.
UR - http://www.scopus.com/inward/record.url?scp=84895725180&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0089014
DO - 10.1371/journal.pone.0089014
M3 - Article
C2 - 24533166
AN - SCOPUS:84895725180
SN - 1932-6203
VL - 9
JO - PLoS ONE
JF - PLoS ONE
IS - 2
M1 - e89014
ER -