Seubert, Peter

Publication Detail

The publication detail shows the title, authors (with indicators showing other profiled authors), information on the publishing organization, abstract and a link to the article in PubMed. This abstract is what is used to create the fingerprint of the publication. If any grants are referenced by the publication, they will be listed here as well.

Characterization of tau fibrillization in vitro.

Shaohua Xu; Kurt R Brunden; John Q Trojanowski; Virginia M-Y Lee (Profiled Authors: Lee, Virginia M-Y; Trojanowski, John Q)

The Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, and Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, USA.
Alzheimer's & dementia : the journal of the Alzheimer's Association 2010;6(2):110-7.

BACKGROUND: The assembly of tau proteins into paired helical filaments, the building blocks of neurofibrillary tangles, is linked to neurodegeneration in Alzheimer's disease and related tauopathies. A greater understanding of this assembly process could identify targets for the discovery of drugs to treat Alzheimer's disease and related disorders. By using recombinant human tau, we have delineated events leading to the conversion of normal soluble tau into tau fibrils. METHODS: Atomic force microscopy and transmission electron microscopy methodologies were used to determine the structure of tau assemblies that formed when soluble tau was incubated with heparin for increasing lengths of time. RESULTS: Tau initially oligomerizes into spherical nucleation units of 18- to 21-nm diameter that appear to assemble linearly into nascent fibrils. Among the earliest tau fibrils are species that resemble a string of beads formed by linearly aligned spheres that with time seem to coalesce to form straight and twisted ribbon-like filaments, as well as paired helical filaments similar to those found in human tauopathies. An analysis of fibril cross sections at later incubation times revealed three fundamental axial structural features. CONCLUSIONS: By monitoring tau fibrillization, we showed that different tau filament morphologies coexist. Temporal changes in the predominant tau structural species suggest that tau fibrillization involves the generation of structural intermediates, resulting in the formation of tau fibrils with verisimilitude to their authentic human counterparts.

3 Originating Grant

• 1.

  LEE, VIRGINIA M

  Frontotemporal Dementias: Genotypes and Phenotypes

  15 March 2000 - 29 February 2016

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 19,741,888

• 2.

  Lee, Virginia M

  In Vitro in Vivo Models of Alzheimer's Disease

  1 September 1997 - 31 August 2008

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 16,839,357

• 3.

  Trojanowski, John Q

  Molecular substrates of aging and neuron death

  15 May 1997 - 30 April 2010

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 24,601,856

Scientific Context

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