title: Aggregate-depleted brain fails to induce Aβ deposition in a mouse model of Alzheimer's disease.
abstract: 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.
authors.affiliation: Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, Texas, United States of America ; Universidad de los Andes, Facultad de Medicina, Santiago, Chile.
authors.forename: Claudia
authors.initials: C
authors.lastname: Duran-Aniotz
authors.affiliation: Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, Texas, United States of America.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Morales
authors.affiliation: Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, Texas, United States of America.
authors.forename: Ines
authors.initials: I
authors.lastname: Moreno-Gonzalez
authors.affiliation: Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, Texas, United States of America ; Education Ministry Key Laboratory on Luminescence and Real-Time Analysis, College of Life Sciences, Southwest University, Chongqing, China.
authors.forename: Ping Ping
authors.initials: PP
authors.lastname: Hu
authors.affiliation: Novartis Vaccines and Diagnostics, Emeryville, California, United States of America.
authors.forename: Joseph
authors.initials: J
authors.lastname: Fedynyshyn
authors.affiliation: Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, Texas, United States of America.
authors.forename: Claudio
authors.initials: C
authors.lastname: Soto
mesh_terms: D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D057786:Peptidomimetics / Q000494:pharmacology*; D066263:Protein Aggregation, Pathological
chemical_list: D016229:Amyloid beta-Peptides; D057786:Peptidomimetics