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In the present study, we analyzed whether tau plays a key role in fibrillar A\u03b2-induced neurite degeneration in central neurons. Cultured hippocampal neurons obtained from wild-type, tau knockout, and human tau transgenic mice were treated with fibrillar A\u03b2. Morphological analysis indicated that neurons expressing either mouse or human tau proteins degenerated in the presence of A\u03b2. On the other hand, tau-depleted neurons showed no signs of degeneration in the presence of A\u03b2. These results provide direct evidence supporting a key role for tau in the mechanisms leading to A\u03b2-induced neurodegeneration in the central nervous system. In addition, the analysis of the composition of the cytoskeleton of tau-depleted neurons suggested that the formation of more dynamic microtubules might confer resistance to A\u03b2-mediated neurodegeneration.<\/jats:p>","DOI":"10.1073\/pnas.092136199","type":"journal-article","created":{"date-parts":[[2002,7,28]],"date-time":"2002-07-28T18:26:28Z","timestamp":1027880788000},"page":"6364-6369","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":701,"title":["Tau is essential to \u03b2-amyloid-induced neurotoxicity"],"prefix":"10.1073","volume":"99","author":[{"given":"Mark","family":"Rapoport","sequence":"first","affiliation":[{"name":"Institute for Neuroscience, Northwestern University, Chicago, IL 60611; Division of Neurology, Department of Medicine, Duke University, Durham, NC 27710; Optimal Screening Vehicles Division, Cognosci, Incorporated, 2 Davis Drive, Research Triangle Park, NC 27709; and Department of Cell and Molecular 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