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Antibodies Raised Against an Aß Oligomer Mimic Recognize Pathological Features in Alzheimer's Disease and Associated Amyloid-Disease Brain Tissue.
Kreutzer, Adam G; Parrocha, Chelsea Marie T; Haerianardakani, Sepehr; Guaglianone, Gretchen; Nguyen, Jennifer T; Diab, Michelle N; Yong, William; Perez-Rosendahl, Mari; Head, Elizabeth; Nowick, James S.
Afiliación
  • Kreutzer AG; Department of Chemistry, University of California Irvine, Irvine, California 92697, United States.
  • Parrocha CMT; Department of Pharmaceutical Sciences, University of California Irvine, Irvine, California 92697, United States.
  • Haerianardakani S; Department of Chemistry, University of California Irvine, Irvine, California 92697, United States.
  • Guaglianone G; Department of Chemistry, University of California Irvine, Irvine, California 92697, United States.
  • Nguyen JT; Department of Pharmaceutical Sciences, University of California Irvine, Irvine, California 92697, United States.
  • Diab MN; Department of Chemistry, University of California Irvine, Irvine, California 92697, United States.
  • Yong W; Department of Pathology and Laboratory Medicine, University of California Irvine, Irvine, California 92697, United States.
  • Perez-Rosendahl M; Department of Pathology and Laboratory Medicine, University of California Irvine, Irvine, California 92697, United States.
  • Head E; Department of Pathology and Laboratory Medicine, University of California Irvine, Irvine, California 92697, United States.
  • Nowick JS; Department of Chemistry, University of California Irvine, Irvine, California 92697, United States.
ACS Cent Sci ; 10(1): 104-121, 2024 Jan 24.
Article en En | MEDLINE | ID: mdl-38292607
ABSTRACT
Antibodies that target the ß-amyloid peptide (Aß) and its associated assemblies are important tools in Alzheimer's disease research and have emerged as promising Alzheimer's disease therapies. This paper reports the creation and characterization of a triangular Aß trimer mimic composed of Aß17-36 ß-hairpins and the generation and study of polyclonal antibodies raised against the Aß trimer mimic. The Aß trimer mimic is covalently stabilized by three disulfide bonds at the corners of the triangular trimer to create a homogeneous oligomer. Structural, biophysical, and cell-based studies demonstrate that the Aß trimer mimic shares characteristics with oligomers of full-length Aß. X-ray crystallography elucidates the structure of the trimer and reveals that four copies of the trimer assemble to form a dodecamer. SDS-PAGE, size exclusion chromatography, and dynamic light scattering reveal that the trimer also forms higher-order assemblies in solution. Cell-based toxicity assays show that the trimer elicits LDH release, decreases ATP levels, and activates caspase-3/7 mediated apoptosis. Immunostaining studies on brain slices from people who lived with Alzheimer's disease and people who lived with Down syndrome reveal that the polyclonal antibodies raised against the Aß trimer mimic recognize pathological features including different types of Aß plaques and cerebral amyloid angiopathy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Risk_factors_studies Idioma: En Revista: ACS Cent Sci Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Risk_factors_studies Idioma: En Revista: ACS Cent Sci Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos