antibodies targeted to the brain with image-guided focused ultrasound reduces amyloid-β plaque load in the tgcrnd8 mouse model of alzheimers disease抗体针对大脑与计算机辅助聚焦超声波降低amyloid-β斑块负荷tgcrnd8阿尔茨海默病小鼠模型.pdfVIP

Antibodies Targeted to the Brain with Image-Guided Focused Ultrasound Reduces Amyloid-b Plaque Load in the TgCRND8 Mouse Model of Alzheimer’s Disease ˜ 1,2,3 1,6 1 2 2,4 Jessica F. Jordao , Carlos A. Ayala-Grosso , Kelly Markham , Yuexi Huang , Rajiv Chopra , JoAnne 3,5 2,4 . 1,3 . McLaurin , Kullervo Hynynen * , Isabelle Aubert * 1 Brain Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada, 2 Imaging, Sunnybrook Research Institute, Toronto, Ontario, Canada, 3 Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada, 4 Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada, 5 Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada, 6 Unidad de ´ Biologıa Molecular, Facultad de Farmacia, Universidad Central de Venezuela, Los Chaguaramos, Caracas, Venezuela Abstract Immunotherapy for Alzheimer’s disease (AD) relies on antibodies directed against toxic amyloid-beta peptide (Ab), which circulate in the bloodstream and remove Ab from the brain [1,2]. In mouse models of AD, the administration of anti-Ab antibodies directly into the brain, in comparison to the bloodstream, was shown to be more efficient at reducing Ab plaque pathology [3,4]. Therefore, delivering anti-Ab antibodies to the brain of AD patients may also improve treatment efficiency. Transcranial focused ultrasound (FUS) is known to transiently-enhance the permeability of the blood-brain barrier (BBB) [5], allowing intravenously admin