early-onset and robust amyloid pathology in a new homozygous mouse model of alzheimers disease早发性和健壮的淀粉样病变的新纯合子小鼠模型阿尔茨海默氏症.pdfVIP

Early-Onset and Robust Amyloid Pathology in a New Homozygous Mouse Model of Alzheimer’s Disease 1 1¤a 1 2 3 Antje Willuweit *, Joachim Velden , Robert Godemann , Andre Manook , Fritz Jetzek , Hartmut 4¤b 4 4 2 2 Tintrup , Gunther Kauselmann , Branko Zevnik , Gjermund Henriksen , Alexander Drzezga , 1¤c 4 1 1 Johannes Pohlner , Michael Schoor , John A. Kemp , Heinz von der Kammer * ¨ ¨ 1 Evotec Neurosciences GmbH, Hamburg, Germany, 2 Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universitat Munchen, Munich, Germany, 3 Evotec Technologies GmbH, Hamburg, Germany, 4 TaconicArtemis GmbH, Cologne, Germany Abstract Background: Transgenic mice expressing mutated amyloid precursor protein (APP) and presenilin (PS)-1 or -2 have been successfully used to model cerebral b-amyloidosis, one of the characteristic hallmarks of Alzheimer’s disease (AD) pathology. However, the use of many transgenic lines is limited by premature death, low breeding efficiencies and late onset and high inter-animal variability of the pathology, creating a need for improved animal models. Here we describe the detailed characterization of a new homozygous double-transgenic mouse line that addresses most of these issues. Meth