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Formation of Neurofibrillary Tangles in P301L Tau Transgenic Mice Induced by Aβ42 Fibrils

Science  24 Aug 2001:
Vol. 293, Issue 5534, pp. 1491-1495
DOI: 10.1126/science.1062097

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Abstract

β-Amyloid plaques and neurofibrillary tangles (NFTs) are the defining neuropathological hallmarks of Alzheimer's disease, but their pathophysiological relation is unclear. Injection of β-amyloid Aβ42 fibrils into the brains of P301L mutant tau transgenic mice caused fivefold increases in the numbers of NFTs in cell bodies within the amygdala from where neurons project to the injection sites. Gallyas silver impregnation identified NFTs that contained tau phosphorylated at serine 212/threonine 214 and serine 422. NFTs were composed of twisted filaments and occurred in 6-month-old mice as early as 18 days after Aβ42injections. Our data support the hypothesis that Aβ42 fibrils can accelerate NFT formation in vivo.

  • * These authors contributed equally to this work.

  • To whom correspondence should be addressed at the Division of Psychiatry Research, University of Zürich, August Forel Strasse 1, 8008 Zürich, Switzerland. E-mail: goetz{at}bli.unizh.ch

  • To whom correspondence should be addressed at the Division of Psychiatry Research, University of Zürich, August Forel Strasse 1, 8008 Zürich, Switzerland. E-mail: nitsch{at}bli.unizh.ch

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