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Science 24 August 2001:
Vol. 293. no. 5534, pp. 1491 - 1495
DOI: 10.1126/science.1062097
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Reports

Formation of Neurofibrillary Tangles in P301L Tau Transgenic Mice Induced by Abeta 42 Fibrils

J. Götz,1*dagger F. Chen,1* J. van Dorpe,2 R. M. Nitsch1ddagger

beta -Amyloid plaques and neurofibrillary tangles (NFTs) are the defining neuropathological hallmarks of Alzheimer's disease, but their pathophysiological relation is unclear. Injection of beta -amyloid Abeta 42 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 Abeta 42 injections. Our data support the hypothesis that Abeta 42 fibrils can accelerate NFT formation in vivo.

1 Division of Psychiatry Research, University of Zürich, August Forel Strasse 1, 8008 Zürich, Switzerland.
2 Experimental Genetics Group, Center for Human Genetics, K. U. Leuven, Campus Gasthuisberg, Leuven, Belgium.
*   These authors contributed equally to this work.

dagger    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

ddagger    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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