Hartman RE, Wozniak DF, Nardi A, Olney JW, Sartorius L, Holtzman DM. Behavioral phenotyping of GFAP-apoE3 and -apoE4 transgenic mice: apoE4 mice show profound working memory impairments in the absence of Alzheimer's-like neuropathology. Exp Neurol. 2001 Aug;170(2):326-44. PubMed.

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  1. This is an important study for two reasons. First, it provides a beautiful example of the kind of work needed to accurately characterize behavioral changes in transgenic mice. The inclusion of details of task and performance data, as well as possible limitations of interpretation, are invaluable. Second, the finding of selective working memory impairments of apoE4 transgenic mice bolsters the hypothesis that apoE may be making its own contribution to cognitive decline in the absence of amyloid deposition. This observation, in conjunction with the transgenic mouse results reported by Buttini et al. (Neurosci. 97:207, 2000), support the view that having apoE4 may be worse than having no apoE at all when considering cognitive performance and neurodegeneration.

    References:

    Buttini M, Akeefe H, Lin C, Mahley RW, Pitas RE, Wyss-Coray T, Mucke L. Dominant negative effects of apolipoprotein E4 revealed in transgenic models of neurodegenerative disease. Neuroscience. 2000;97(2):207-10. PubMed.

    View all comments by Keith Crutcher

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