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

Research output: Contribution to journalArticle

409 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 languageEnglish (US)
Pages (from-to)191-199
Number of pages9
JournalNeuron
Volume47
Issue number2
DOIs
StatePublished - Jul 21 2005

ASJC Scopus subject areas

  • Neuroscience(all)

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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