Aβ is targeted to the vasculature in a mouse model of hereditary cerebral hemorrhage with amyloidosis

We found that neuronal overexpression of human E693Q amyloid beta precursor protein in mice caused extensive cerebral amyloid angiopathy, smooth muscle cell degeneration, hemorrhages and neuroinflammation

Martin C Herzig; David T Winkler; Patrick Burgermeister; Michelle Pfeifer; Esther Kohler; Stephen D Schmidt; Simone Danner; Dorothee Abramowski; Christine Stürchler-Pierrat; Kurt Bürki; Sjoerd G van Duinen; Marion L C Maat-Schieman; Matthias Staufenbiel; Paul M Mathews; Mathias Jucker


Scholarcy highlights

  • The E693Q mutation in the amyloid beta precursor protein leads to cerebral amyloid angiopathy, with recurrent cerebral hemorrhagic strokes and dementia
  • In contrast to Alzheimer disease, the brains of those affected by hereditary cerebral hemorrhage with amyloidosis-Dutch type show few parenchymal amyloid plaques
  • We found that neuronal overexpression of human E693Q APP in mice caused extensive CAA, smooth muscle cell degeneration, hemorrhages and neuroinflammation
  • Immunohistochemical staining with C terminus–specific antibodies to amyloid-β peptides suggest that amyloid-β40 peptide predominates over Aβ42 in the cerebrovascular amyloid
  • DISCUSSION the APP mutation that causes HCHWA-D was identified more than a decade ago, progress toward understanding the pathogenesis of HCHWA-D has been hampered by the absence of an animal model
  • The observation that neuronal expression of APPDutch is sufficient for cerebrovascular amyloidosis, smooth muscle cell degeneration and hemorrhage in a mouse model strongly suggests that neurons are the source of the cerebrovascular amyloid in HCHWA-D
  • Cerebral amyloid-β peptides levels of patients and Aβ-depositing mice were assayed by sandwich ELISA from formic acid–extracted sucrose homogenates prepared from postmortem human cortical tissue or mouse hemi-brains lacking the cerebellum, as previously described

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