Sci. Aging Knowl. Environ., 3 October 2001
Vol. 2001, Issue 1, p. or4


Enhanced Neurofibrillary Degeneration in Transgenic Mice Expressing Mutant Tau and APP

Jada Lewis, Dennis W. Dickson, Wen-Lang Lin, Louise Chisholm, Anthony Corral, Graham Jones, Shu-Hui Yen, Naruhiko Sahara, Lisa Skipper, Debra Yager, Chris Eckman, John Hardy, Mike Hutton, and Eileen McGowan;2001/1/or4

Abstract: Science 293, 1487-1491 (2001).

JNPL3 transgenic mice expressing a mutant tau protein, which develop neurofibrillary tangles and progressive motor disturbance, were crossed with Tg2576 transgenic mice expressing mutant {beta}-amyloid precursor protein (APP), thus modulating the APP-A{beta} ({beta}-amyloid peptide) environment. The resulting double mutant (tau/APP) progeny and the Tg2576 parental strain developed A{beta} deposits at the same age; however, relative to JNPL3 mice, the double mutants exhibited neurofibrillary tangle pathology that was substantially enhanced in the limbic system and olfactory cortex. These results indicate that either APP or A{beta} influences the formation of neurofibrillary tangles. The interaction between A{beta} and tau pathologies in these mice supports the hypothesis that a similar interaction occurs in Alzheimer's disease.

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Science of Aging Knowledge Environment. ISSN 1539-6150