Report

Enhanced Neurofibrillary Degeneration in Transgenic Mice Expressing Mutant Tau and APP

Science  24 Aug 2001:
Vol. 293, Issue 5534, pp. 1487-1491
DOI: 10.1126/science.1058189

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Abstract

JNPL3 transgenic mice expressing a mutant tau protein, which develop neurofibrillary tangles and progressive motor disturbance, were crossed with Tg2576 transgenic mice expressing mutant β-amyloid precursor protein (APP), thus modulating the APP-Aβ (β-amyloid peptide) environment. The resulting double mutant (tau/APP) progeny and the Tg2576 parental strain developed Aβ 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 Aβ influences the formation of neurofibrillary tangles. The interaction between Aβ and tau pathologies in these mice supports the hypothesis that a similar interaction occurs in Alzheimer's disease.

  • * These authors contributed equally to this report.

  • To whom correspondence should be addressed. E-mail: hutton.michael{at}mayo.edu

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