Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 7-Day Trial for You or Your Team.

Learn More →

Alzheimer's disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules

Alzheimer's disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and... Microtubule–associated protein tau becomes abnormally hyperphosphorylated in Alzheimer's disease (AD) and accumulates as tangles of paired helical filaments in neurons undergoing degeneration. We now show that in solution normal tau associates with the AD hyperphosphorylated tau (AD P–tau) in a nonsaturable fashion, forming large tangles of filaments 3.3 ± 0.7 nm in diameter. These tangles, which are not detected in identically treated normal tau or AD P–tau alone, are made up of filaments several microns in length and are labeled with tau antibodies. Dephosphorylation with alkaline phosphatase abolishes the ability of AD P–tau to aggregate with normal tau and prevents tangle formation. AD P–tau disassembles microtubules assembled from normal tau and tubulin. These data provide insight into how the hyperphosphorylation of tau might lead to the formation of the neurofibrillary tangles and the degeneration of the affected neurons in AD. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Medicine Springer Journals

Alzheimer's disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules

Download PDF
5 pages

Loading next page...
 
/lp/springer-journals/alzheimer-s-disease-hyperphosphorylated-tau-sequesters-normal-tau-into-QukKI013mA

References (33)

Publisher
Springer Journals
Copyright
Copyright © 1996 by Nature Publishing Group
Subject
Biomedicine; Biomedicine, general; Cancer Research; Metabolic Diseases; Infectious Diseases; Molecular Medicine; Neurosciences
ISSN
1078-8956
eISSN
1546-170X
DOI
10.1038/nm0796-783
Publisher site
See Article on Publisher Site

Abstract

Microtubule–associated protein tau becomes abnormally hyperphosphorylated in Alzheimer's disease (AD) and accumulates as tangles of paired helical filaments in neurons undergoing degeneration. We now show that in solution normal tau associates with the AD hyperphosphorylated tau (AD P–tau) in a nonsaturable fashion, forming large tangles of filaments 3.3 ± 0.7 nm in diameter. These tangles, which are not detected in identically treated normal tau or AD P–tau alone, are made up of filaments several microns in length and are labeled with tau antibodies. Dephosphorylation with alkaline phosphatase abolishes the ability of AD P–tau to aggregate with normal tau and prevents tangle formation. AD P–tau disassembles microtubules assembled from normal tau and tubulin. These data provide insight into how the hyperphosphorylation of tau might lead to the formation of the neurofibrillary tangles and the degeneration of the affected neurons in AD.

Journal

Nature Medicine – Springer Journals

Published: Jul 1, 1996

There are no references for this article.