Over the years, extensive progress has been made in the characterization of tau and its role in the fibrillar pathology of Alzheimer's disease and other tauopathies. Many biochemical models for the self assembly of tau have been used to further ascertain some of the fundamental properties of tau filament assembly. For example, multiple groups have identified which domains on the tau molecule are required for filament polymerization. At present, however, little is known about how tau filaments that characterize a number of neurodegenerative diseases form within neurons and glia. A primary goal of this proposal will be to design a human cell culture system for tau filament accumulation, and to characterize the impact of tau filament accumulation on cell function. The primary hindrance to tau filament assembly -- de novo nucleation of filaments -- will be bypassed by microinjecting pre-assembled tau filaments into cell lines stably expressing transfected tau. These experiments will provide insight into the stability of intracellular tau filaments and determine if tau filaments are relatively inert, as has been proposed in the lamprey model of tau filament accumulation, or whether tau filaments can have a significant impact upon basic cellular function.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AG020465-02
Application #
6613467
Study Section
Special Emphasis Panel (ZRG1-F03A (20))
Program Officer
Snyder, Stephen D
Project Start
2002-07-25
Project End
2005-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
2
Fiscal Year
2003
Total Cost
$46,420
Indirect Cost
Name
University of Virginia
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
King, Michelle E; Kan, Ho-Man; Baas, Peter W et al. (2006) Tau-dependent microtubule disassembly initiated by prefibrillar beta-amyloid. J Cell Biol 175:541-6
King, Michelle E (2005) Can tau filaments be both physiologically beneficial and toxic? Biochim Biophys Acta 1739:260-7