Journal of Cell Science, Vol 113, Issue 8 1373-1387, Copyright © 2000 by Company of Biologists

JOURNAL ARTICLES

Human tau filaments induce microtubule and synapse loss in an in vivo model of neurofibrillary degenerative disease

GF Hall, B Chu, G Lee and J Yao
Department of Biological Sciences, University of Massachusetts, Lowell, Massachusetts 01854, USA. garth_hall@uml.edu

The intracellular accumulation of tau protein and its aggregation into filamentous deposits is the intracellular hallmark of neurofibrillary degenerative diseases such as Alzheimer's Disease and familial tauopathies in which tau is now thought to play a critical pathogenic role. Until very recently, the lack of a cellular model in which human tau filaments can be experimentally generated has prevented direct investigation of the causes and consequences of tau filament formation in vivo. In this study, we show that human tau filaments formed in lamprey central neurons (ABCs) that chronically overexpress human tau resemble the 'straight filaments' seen in Alzheimer's Disease and other neurofibrillary conditions, and are distinguishable from neurofilaments by their ultrastructure, distribution and intracellular behavior. We also show that tau filament formation in ABCs is associated with a distinctive pattern of dendritic degeneration that closely resembles the cytopathology of human neurofibrillary degenerative disease. This pattern includes localized cytoskeletal disruption and aggregation of membranous organelles, distal dendritic beading, and the progressive loss of dendritic microtubules and synapses. These results suggest that tau filament formation may be responsible for many key cytopathological features of neurofibrillary degeneration, possibly via the loss of microtubule based intracellular transport.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				A. Deshpande, K. M. Win, and J. Busciglio Tau isoform expression and regulation in human cortical neurons FASEB J, July 1, 2008; 22(7): 2357 - 2367. [Abstract] [Full Text] [PDF]

				S. M. Greenwood, S. M. Mizielinska, B. G. Frenguelli, J. Harvey, and C. N. Connolly Mitochondrial Dysfunction and Dendritic Beading during Neuronal Toxicity J. Biol. Chem., September 7, 2007; 282(36): 26235 - 26244. [Abstract] [Full Text] [PDF]

				S. F. Levy, A. C. LeBoeuf, M. R. Massie, M. A. Jordan, L. Wilson, and S. C. Feinstein Three- and Four-repeat Tau Regulate the Dynamic Instability of Two Distinct Microtubule Subpopulations in Qualitatively Different Manners: IMPLICATIONS FOR NEURODEGENERATION J. Biol. Chem., April 8, 2005; 280(14): 13520 - 13528. [Abstract] [Full Text] [PDF]

				J. AVILA, J. J. LUCAS, M. PEREZ, and F. HERNANDEZ Role of Tau Protein in Both Physiological and Pathological Conditions Physiol Rev, April 1, 2004; 84(2): 361 - 384. [Abstract] [Full Text] [PDF]

				Y. Yoshiyama, B. Zhang, J. Bruce, J. Q. Trojanowski, and V. M.-Y. Lee Reduction of Detyrosinated Microtubules and Golgi Fragmentation Are Linked to Tau-Induced Degeneration in Astrocytes J. Neurosci., November 19, 2003; 23(33): 10662 - 10671. [Abstract] [Full Text] [PDF]

				V. M.-Y. Lee and J. Q. Trojanowski Transgenic mouse models of tauopathies: Prospects for animal models of Pick's disease Neurology, June 12, 2001; 56(90004): S26 - 30. [Abstract] [Full Text] [PDF]

				K. Spittaels, C. Van den Haute, J. Van Dorpe, H. Geerts, M. Mercken, K. Bruynseels, R. Lasrado, K. Vandezande, I. Laenen, T. Boon, et al. Glycogen Synthase Kinase-3beta Phosphorylates Protein Tau and Rescues the Axonopathy in the Central Nervous System of Human Four-repeat Tau Transgenic Mice J. Biol. Chem., December 22, 2000; 275(52): 41340 - 41349. [Abstract] [Full Text] [PDF]