Aβ42 is essential for parenchymal and vascular amyloid deposition in mice

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

doi:10.1016/j.neuron.2005.06.030

Aβ42 is essential for parenchymal and vascular amyloid deposition in mice

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

Neuroscience

Research output: Contribution to journal › Article › peer-review

439 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	191-199
Number of pages	9
Journal	Neuron
Volume	47
Issue number	2
DOIs	https://doi.org/10.1016/j.neuron.2005.06.030
State	Published - Jul 21 2005

ASJC Scopus subject areas

General Neuroscience

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10.1016/j.neuron.2005.06.030

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McGowan, E., Pickford, F., Kim, J., Onstead, L., Eriksen, J., Yu, C., Skipper, L., Murphy, M. P., Beard, J., Das, P., Jansen, K., DeLucia, M., Lin, W. L., Dolios, G., Wang, R., Eckman, C. B., Dickson, D. W., Hutton, M., Hardy, J., & Golde, T. (2005). Aβ42 is essential for parenchymal and vascular amyloid deposition in mice. Neuron, 47(2), 191-199. https://doi.org/10.1016/j.neuron.2005.06.030

McGowan, E, Pickford, F, Kim, J, Onstead, L, Eriksen, J, Yu, C, Skipper, L, Murphy, MP, Beard, J, Das, P, Jansen, K, DeLucia, M, Lin, WL, Dolios, G, Wang, R, Eckman, CB, Dickson, DW, Hutton, M, Hardy, J & Golde, T 2005, 'Aβ42 is essential for parenchymal and vascular amyloid deposition in mice', Neuron, vol. 47, no. 2, pp. 191-199. https://doi.org/10.1016/j.neuron.2005.06.030

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title = "Aβ42 is essential for parenchymal and vascular amyloid deposition in mice",

abstract = "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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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

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Aβ42 is essential for parenchymal and vascular amyloid deposition in mice

Abstract

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