title: Soluble Amyloid-beta Aggregates from Human Alzheimer's Disease Brains.
abstract: Soluble amyloid-beta (Aβ) aggregates likely contribute substantially to the dementia that characterizes Alzheimer's disease. However, despite intensive study of in vitro preparations and animal models, little is known about the characteristics of soluble Aβ aggregates in the human Alzheimer's disease brain. Here we present a new method for extracting soluble Aβ aggregates from human brains, separating them from insoluble aggregates and Aβ monomers using differential ultracentrifugation, and purifying them >6000 fold by dual antibody immunoprecipitation. The method resulted in <40% loss of starting material, no detectible ex vivo aggregation of monomeric Aβ, and no apparent ex vivo alterations in soluble aggregate sizes. By immunoelectron microscopy, soluble Aβ aggregates typically appear as clusters of 10-20 nanometer diameter ovoid structures with 2-3 amino-terminal Aβ antibody binding sites, distinct from previously characterized structures. This approach may facilitate investigation into the characteristics of native soluble Aβ aggregates, and deepen our understanding of Alzheimer's dementia.
authors.affiliation: Department of Neurology, 660 South Euclid Avenue, Box 8111, Washington University, St. Louis, Missouri, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Esparza
authors.affiliation: Department of Neurology, 660 South Euclid Avenue, Box 8111, Washington University, St. Louis, Missouri, USA.
authors.forename: Norelle C
authors.initials: NC
authors.lastname: Wildburger
authors.affiliation: Department of Neurology, 660 South Euclid Avenue, Box 8111, Washington University, St. Louis, Missouri, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Biomedical Engineering, Washington University, St. Louis, Missouri, USA.
authors.forename: Mihika
authors.initials: M
authors.lastname: Gangolli
authors.affiliation: Department of Neurology, 660 South Euclid Avenue, Box 8111, Washington University, St. Louis, Missouri, USA.|The Knight Alzheimer's Disease Research Center, Washington University, St. Louis, Missouri, USA.|Hope Center for Neurological Disorders, Washington University, St. Louis, Missouri, USA.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Cairns
authors.affiliation: Department of Neurology, 660 South Euclid Avenue, Box 8111, Washington University, St. Louis, Missouri, USA.|The Knight Alzheimer's Disease Research Center, Washington University, St. Louis, Missouri, USA.|Hope Center for Neurological Disorders, Washington University, St. Louis, Missouri, USA.
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Bateman
authors.affiliation: Department of Neurology, 660 South Euclid Avenue, Box 8111, Washington University, St. Louis, Missouri, USA.|Department of Biomedical Engineering, Washington University, St. Louis, Missouri, USA.|Hope Center for Neurological Disorders, Washington University, St. Louis, Missouri, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Brody
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D005260:Female; D006801:Humans; D008297:Male; D066263:Protein Aggregation, Pathological / Q000378:metabolism*; D012995:Solubility
chemical_list: D016229:Amyloid beta-Peptides