Aβ42 Is Essential for Parenchymal and Vascular Amyloid Deposition in Mice

نویسندگان

  • Eileen McGowan
  • Fiona Pickford
  • Jungsu Kim
  • Luisa Onstead
  • Jason Eriksen
  • Cindy Yu
  • Lisa Skipper
  • M. Paul Murphy
  • Jenny Beard
  • Pritam Das
  • Karen Jansen
  • Michael DeLucia
  • Wen-Lang Lin
  • Georgia Dolios
  • Rong Wang
  • Christopher B. Eckman
  • Dennis W. Dickson
  • Mike Hutton
  • John Hardy
  • Todd Golde
چکیده

Considerable circumstantial evidence suggests that Abeta42 is the initiating molecule in Alzheimer's disease (AD) pathogenesis. However, the absolute requirement for Abeta42 for amyloid deposition has never been demonstrated in vivo. We have addressed this by developing transgenic models that express Abeta1-40 or Abeta1-42 in the absence of human amyloid beta protein precursor (APP) overexpression. Mice expressing high levels of Abeta1-40 do not develop overt amyloid pathology. In contrast, mice expressing lower levels of Abeta1-42 accumulate insoluble Abeta1-42 and develop compact amyloid plaques, congophilic amyloid angiopathy (CAA), and diffuse Abeta deposits. When mice expressing Abeta1-42 are crossed with mutant APP (Tg2576) mice, there is also a massive increase in amyloid deposition. These data establish that Abeta1-42 is essential for amyloid deposition in the parenchyma and also in vessels.

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عنوان ژورنال:
  • Neuron

دوره 47  شماره 

صفحات  -

تاریخ انتشار 2005