Your browser doesn't support javascript.
loading
APOE Christchurch-mimetic therapeutic antibody reduces APOE-mediated toxicity and tau phosphorylation.
Marino, Claudia; Perez-Corredor, Paula; O'Hare, Michael; Heuer, Annie; Chmielewska, Natalia; Gordon, Harper; Chandrahas, Anita S; Gonzalez-Buendia, Lucia; Delgado-Tirado, Santiago; Doan, Tri H; Vanderleest, Timothy E; Arevalo-Alquichire, Said; Obar, Robert A; Ortiz-Cordero, Carolina; Villegas, Andres; Sepulveda-Falla, Diego; Kim, Leo A; Lopera, Francisco; Mahley, Robert; Huang, Yadong; Quiroz, Yakeel T; Arboleda-Velasquez, Joseph F.
Afiliación
  • Marino C; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, Massachusetts, USA.
  • Perez-Corredor P; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, Massachusetts, USA.
  • O'Hare M; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, Massachusetts, USA.
  • Heuer A; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, Massachusetts, USA.
  • Chmielewska N; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, Massachusetts, USA.
  • Gordon H; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, Massachusetts, USA.
  • Chandrahas AS; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, Massachusetts, USA.
  • Gonzalez-Buendia L; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, Massachusetts, USA.
  • Delgado-Tirado S; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, Massachusetts, USA.
  • Doan TH; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, Massachusetts, USA.
  • Vanderleest TE; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, Massachusetts, USA.
  • Arevalo-Alquichire S; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, Massachusetts, USA.
  • Obar RA; Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA.
  • Ortiz-Cordero C; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
  • Villegas A; Grupo de Neurociencias de Antioquia, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
  • Sepulveda-Falla D; Molecular Neuropathology of Alzheimer's Disease, Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Kim LA; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, Massachusetts, USA.
  • Lopera F; Grupo de Neurociencias de Antioquia, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
  • Mahley R; Gladstone Institute of Neurological Disease, San Francisco, California, USA.
  • Huang Y; Gladstone Institute of Cardiovascular Disease, San Francisco, California, USA.
  • Quiroz YT; Department of Pathology, UCSF, San Francisco, California, USA.
  • Arboleda-Velasquez JF; Department of Medicine, UCSF, San Francisco, California, USA.
Alzheimers Dement ; 20(2): 819-836, 2024 Feb.
Article en En | MEDLINE | ID: mdl-37791598
INTRODUCTION: We discovered that the APOE3 Christchurch (APOE3Ch) variant may provide resistance to Alzheimer's disease (AD). This resistance may be due to reduced pathological interactions between ApoE3Ch and heparan sulfate proteoglycans (HSPGs). METHODS: We developed and characterized the binding, structure, and preclinical efficacy of novel antibodies targeting human ApoE-HSPG interactions. RESULTS: We found that one of these antibodies, called 7C11, preferentially bound ApoE4, a major risk factor for sporadic AD, and disrupts heparin-ApoE4 interactions. We also determined the crystal structure of a Fab fragment of 7C11 and used computer modeling to predict how it would bind to ApoE. When we tested 7C11 in mouse models, we found that it reduced recombinant ApoE-induced tau pathology in the retina of MAPT*P301S mice and curbed pTau S396 phosphorylation in brains of systemically treated APOE4 knock-in mice. Targeting ApoE-HSPG interactions using 7C11 antibody may be a promising approach to developing new therapies for AD.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Apolipoproteína E4 / Enfermedad de Alzheimer Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Alzheimers Dement 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 Asunto principal: Apolipoproteína E4 / Enfermedad de Alzheimer Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Alzheimers Dement Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos