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Open Access 01-05-2007 | Original Paper

Disruption of microtubule network by Alzheimer abnormally hyperphosphorylated tau

Authors: Bin Li, Muhammad Omar Chohan, Inge Grundke-Iqbal, Khalid Iqbal

Published in: Acta Neuropathologica | Issue 5/2007

Abstract

Hyperphosphorylated tau has long been proposed as the key molecule disrupting normal neuronal microtubule dynamics and leading to neurofibrillary degeneration in Alzheimer disease. Here we provide a direct evidence of hyperphosphorylated tau-induced disruption of microtubule network. Using Nocodozole-treated and detergent-extracted cells, we created a neuronal environment in mouse embryonic fibroblasts, 3T3 cells, by replacing their cytoplasm with adult rat brain cytosol. By recreating neuronal microtubule network in these cells, we were able to follow the effects of hyperphosphorylated tau on microtubule dynamics in real time. Whereas recombinant human brain tau promoted assembly and bundling of microtubules, abnormally hyperphosphorylated tau isolated from Alzheimer disease brain cytosol (AD P-tau) inhibited the assembly and disrupted preformed microtubule network by sequestering normal brain tau and MAP2. This breakdown of the microtubule network was reversed by treatment of the extracted cells with protein phosphatase-2A. This study, for the first time, provides direct mechanistic insights into the molecular basis of both axonal and dendritic neurodegeneration seen in Alzheimer disease.

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Title: Disruption of microtubule network by Alzheimer abnormally hyperphosphorylated tau
Authors: Bin Li
Muhammad Omar Chohan
Inge Grundke-Iqbal
Khalid Iqbal
Publication date: 01-05-2007
Publisher: Springer-Verlag
Published in: Acta Neuropathologica / Issue 5/2007
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-007-0207-8

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Disruption of microtubule network by Alzheimer abnormally hyperphosphorylated tau

Abstract

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Abstract

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