TY - JOUR
T1 - Aβ42 is essential for parenchymal and vascular amyloid deposition in mice
AU - McGowan, Eileen
AU - Pickford, Fiona
AU - Kim, Jungsu
AU - Onstead, Luisa
AU - Eriksen, Jason
AU - Yu, Cindy
AU - Skipper, Lisa
AU - Murphy, M. Paul
AU - Beard, Jenny
AU - Das, Pritam
AU - Jansen, Karen
AU - DeLucia, Michael
AU - Lin, Wen Lang
AU - Dolios, Georgia
AU - Wang, Rong
AU - Eckman, Christopher B.
AU - Dickson, Dennis W.
AU - Hutton, Mike
AU - Hardy, John
AU - Golde, Todd
PY - 2005/7/21
Y1 - 2005/7/21
N2 - Considerable circumstantial evidence suggests that Aβ42 is the initiating molecule in Alzheimer's disease (AD) pathogenesis. However, the absolute requirement for Aβ42 for amyloid deposition has never been demonstrated in vivo. We have addressed this by developing transgenic models that express Aβ1-40 or Aβ1-42 in the absence of human amyloid β protein precursor (APP) overexpression. Mice expressing high levels of Aβ1-40 do not develop overt amyloid pathology. In contrast, mice expressing lower levels of Aβ1-42 accumulate insoluble Aβ1-42 and develop compact amyloid plaques, congophilic amyloid angiopathy (CAA), and diffuse Aβ deposits. When mice expressing Aβ1-42 are crossed with mutant APP (Tg2576) mice, there is also a massive increase in amyloid deposition. These data establish that Aβ1-42 is essential for amyloid deposition in the parenchyma and also in vessels.
AB - Considerable circumstantial evidence suggests that Aβ42 is the initiating molecule in Alzheimer's disease (AD) pathogenesis. However, the absolute requirement for Aβ42 for amyloid deposition has never been demonstrated in vivo. We have addressed this by developing transgenic models that express Aβ1-40 or Aβ1-42 in the absence of human amyloid β protein precursor (APP) overexpression. Mice expressing high levels of Aβ1-40 do not develop overt amyloid pathology. In contrast, mice expressing lower levels of Aβ1-42 accumulate insoluble Aβ1-42 and develop compact amyloid plaques, congophilic amyloid angiopathy (CAA), and diffuse Aβ deposits. When mice expressing Aβ1-42 are crossed with mutant APP (Tg2576) mice, there is also a massive increase in amyloid deposition. These data establish that Aβ1-42 is essential for amyloid deposition in the parenchyma and also in vessels.
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U2 - 10.1016/j.neuron.2005.06.030
DO - 10.1016/j.neuron.2005.06.030
M3 - Article
C2 - 16039562
AN - SCOPUS:22544482926
VL - 47
SP - 191
EP - 199
IS - 2
ER -