Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2004 Oct;25(9):1153-67.
doi: 10.1016/j.neurobiolaging.2003.12.011.

Cognitive impairment in PDAPP mice depends on ApoE and ACT-catalyzed amyloid formation

Lars N G Nilsson  1 , Gary W Arendash, Ralph E Leighty, David A Costa, Mark A Low, Marcos F Garcia, Jennifer R Cracciolo, Amyn Rojiani, Xin Wu, Kelly R Bales, Steven M Paul, Huntington Potter
Affiliations
Comparative Study

Cognitive impairment in PDAPP mice depends on ApoE and ACT-catalyzed amyloid formation

Lars N G Nilsson et al. Neurobiol Aging. 2004 Oct.

Abstract

Biochemical and genetic studies indicate that the inflammatory proteins, apolipoprotein E (ApoE) and alpha(1)-antichymotrypsin (ACT) are important in the pathogenesis of Alzheimer's disease (AD). Using several lines of multiply transgenic/knockout mice we show here that murine ApoE and human ACT separately and synergistically facilitate both diffuse A beta immunoreactive and fibrillar amyloid deposition and thus also promote cognitive impairment in aged PDAPP(V717F) mice. The degree of cognitive impairment is highly correlated with the ApoE- and ACT-dependent hippocampal amyloid burden, with PDAPP mice lacking ApoE and ACT having little amyloid and little learning disability. A analysis of young mice before the onset of amyloid formation shows that steady-state levels of monomeric A beta peptide are unchanged by ApoE or ACT. These data suggest that the process or product of amyloid formation is more critical than monomeric A beta for the neurological decline in AD, and that the risk factors ApoE and ACT participate primarily in disease processes downstream of APP processing.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources