Further evidence that ApoE is needed for deposition of the fibrillar form of Aβ in plaques was presented today at the American Neurological Association's annual meeting in Seattle today. David Holtzman and his colleagues at Washington University in St. Louis, Missouri, described their experiments crossing ApoE knockout mice with the APPsw mouse model of Alzheimer's disease developed by Karen Hsiao and colleagues at the University of Minnesota.

The APPsw mouse features Aβ deposition in the brain, as well as within blood vessels in the brain. Similar to their findings with the PDAPP mouse model (Holtzman et al., published earlier this year), the researchers found that murine ApoE was required for the deposition of fibrillar Aβ in the brain. They also found that ApoE was required for fibrillar Aβ deposition in blood vessels. Finally, only in the mice with ApoE did they find neuritic plaques consisting of fibrillar Aβ. APPsw mice without ApoE did develop some Aβ deposition but it was not fibrillar and was not associated with neuritic degeneration.

Said Holtzman, "This finding strongly suggests that ApoE is needed for the conversion of amyloid-β to a fibrillar form, which in turn is required to damage nerve cell processes in a living brain." Currently underway are experiments to introduce human ApoE isoforms into these mouse models of Alzheimer's.—Hakon Heimer

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References

Paper Citations

  1. . Expression of human apolipoprotein E reduces amyloid-beta deposition in a mouse model of Alzheimer's disease. J Clin Invest. 1999 Mar;103(6):R15-R21. PubMed.

Further Reading

Papers

  1. . Expression of human apolipoprotein E reduces amyloid-beta deposition in a mouse model of Alzheimer's disease. J Clin Invest. 1999 Mar;103(6):R15-R21. PubMed.