Tau is essential to beta -amyloid-induced neurotoxicity.

Journal Article (Journal Article)

Senile plaques and neurofibrillary tangles, the two hallmark lesions of Alzheimer's disease, are the results of the pathological deposition of proteins normally present throughout the brain. Senile plaques are extracellular deposits of fibrillar beta-amyloid peptide (Abeta); neurofibrillary tangles represent intracellular bundles of self-assembled hyperphosphorylated tau proteins. Although these two lesions are often present in the same brain areas, a mechanistic link between them has yet to be established. In the present study, we analyzed whether tau plays a key role in fibrillar Abeta-induced neurite degeneration in central neurons. Cultured hippocampal neurons obtained from wild-type, tau knockout, and human tau transgenic mice were treated with fibrillar Abeta. Morphological analysis indicated that neurons expressing either mouse or human tau proteins degenerated in the presence of Abeta. On the other hand, tau-depleted neurons showed no signs of degeneration in the presence of Abeta. These results provide direct evidence supporting a key role for tau in the mechanisms leading to Abeta-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 Abeta-mediated neurodegeneration.

Full Text

Duke Authors

Cited Authors

  • Rapoport, M; Dawson, HN; Binder, LI; Vitek, MP; Ferreira, A

Published Date

  • April 30, 2002

Published In

Volume / Issue

  • 99 / 9

Start / End Page

  • 6364 - 6369

PubMed ID

  • 11959919

Pubmed Central ID

  • PMC122954

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.092136199


  • eng

Conference Location

  • United States