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Originally published online as doi:10.2353/ajpath.2009.080790 on February 13, 2009

Published online before print February 13, 2009
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(American Journal of Pathology. 2009;174:722-726.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.080790

Short Communications

E22Q-Mutant Aβ Peptide (AβDutch) Increases Vascular but Reduces Parenchymal Aβ Deposition

Martin C. Herzig*, Yvonne S. Eisele*{dagger}, Matthias Staufenbiel{ddagger} and Mathias Jucker*

From the Department of Cellular Neurology,* Hertie Institute for Clinical Brain Research, and the Graduate School of Cellular and Molecular Neuroscience,{dagger} University of Tübingen, Tübingen, Germany; and the Nervous System Research,{ddagger} Novartis Institutes for Biomedical Research, Basel, Switzerland

Patients that have hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D) generate both wild-type β-amyloid (Aβwt) and E22Q-mutant β-amyloid (AβDutch). Postmortem analysis of HCHWA-D brains reveals severe cerebral amyloid angiopathy with very little parenchymal amyloid deposition. To investigate amyloidosis in the presence of both Aβwt and AβDutch variants, transgenic (tg) APP23 mice were crossed with APPDutch mice. Although single-tg APP23 mice deposited Aβwt with aging, double-tg APP23/APPDutch mice co-deposited AβDutch (mainly AβDutch1-40) and Aβwt at twofold higher total Aβ levels. Vascular Aβ deposits and hemorrhages were twice as high in APP23/APPDutch mice compared with APP23 mice. Surprisingly, parenchymal Aβ deposition was reduced in the double-tg mice compared with the single-tg APP23 mice. Our findings suggest that AβDutch1-40 inhibits parenchymal amyloidosis but exacerbates vascular amyloid, hence explaining the compartment-specific distribution of cerebral amyloid in HCHWA-D patients.






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Copyright © 2009 by the American Society for Investigative Pathology.