A role for apoE in regulating the levels of α-1-antichymotrypsin in the aging mouse brain and in Alzheimer's disease

Federico Licastro, Iain L. Campbell, Carrie Kincaid, Isaac Veinbergs, Emily Van Uden, Edward Rockenstein, Margaret Mallory, John R. Gilbert, Eliezer Masliah

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

This study was designed to explore the possible functional relationships between apolipoprotein E (apoE) and the protease inhibitor α-1- antichymotrypsin in the aging mouse brain and in Alzheimer's disease. For this purpose, levels of EB22/5 (the mouse homologue to human α-1- antichymotrypsin) mRNA expression was studied in apoE-deficient mice. These mice showed an age-dependent increase of EB22/5 mRNA expression in the brain. Furthermore, overexpression of allele 3 of human APOE gene in transgenic mice (in an apoE-deficient background) resulted in normalization of levels of EB22/5 mRNA expression compatible with levels found in control mice. In contrast, overexpression of human APOE4 allele or down-regulation of the apoE receptor low density lipoprotein receptor-related protein by deletion of the receptor-associated protein was associated with elevated levels of EB22/5 similar to apoE-deficient mice. Consistent with the findings in murine models, human α-1-antichymotrypsin protein was increased in brain homogenates from patients with Alzheimer's disease, and levels of this serpin were the highest in patients with the APOE4 allele. In summary, the present study showed evidence supporting a role for apoE in regulating α-1- antichymotrypsin expression. This is relevant to Alzheimer's disease because these two molecules appear to be closely associated with the pathogenesis of this disorder.

Original languageEnglish (US)
Pages (from-to)869-875
Number of pages7
JournalAmerican Journal of Pathology
Volume155
Issue number3
DOIs
StatePublished - Sep 1999

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Licastro, F., Campbell, I. L., Kincaid, C., Veinbergs, I., Van Uden, E., Rockenstein, E., Mallory, M., Gilbert, J. R., & Masliah, E. (1999). A role for apoE in regulating the levels of α-1-antichymotrypsin in the aging mouse brain and in Alzheimer's disease. American Journal of Pathology, 155(3), 869-875. https://doi.org/10.1016/S0002-9440(10)65186-3