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

Garth F Hall; Boyang Chu; Gloria Lee; Jun Yao

doi:10.1242/jcs.113.8.1373

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

Journal article

Peer reviewed

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

Garth F Hall, Boyang Chu, Gloria Lee and Jun Yao

Journal of cell science, Vol.113 (8), pp.1373-1387

04/2000

DOI: 10.1242/jcs.113.8.1373

PMID: 10725221

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Abstract

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.

Gene Expression

Transfection

Humans

Synapses - ultrastructure

Synapses - pathology

Microscopy, Electron

Microtubules - pathology

Alzheimer Disease - pathology

Lampreys

tau Proteins - biosynthesis

Microtubules - metabolism

Animals

Synapses - metabolism

tau Proteins - genetics

Alzheimer Disease - metabolism

Microtubules - ultrastructure

Disease Models, Animal

Details

Title: Subtitle: Human tau filaments induce microtubule and synapse loss in an in vivo model of neurofibrillary degenerative disease
Creators: Garth F Hall - Department of Biological Sciences, University of Massachusetts, Lowell, Massachusetts 01854, USA. garth_hall@uml.edu
Boyang Chu
Gloria Lee
Jun Yao
Resource Type: Journal article
Publication Details: Journal of cell science, Vol.113 (8), pp.1373-1387
DOI: 10.1242/jcs.113.8.1373
PMID: 10725221
NLM abbreviation: J Cell Sci
ISSN: 0021-9533
eISSN: 1477-9137
Publisher: England
Grant note: AG13919 / NIA NIH HHS
Language: English
Date published: 04/2000
Academic Unit: Iowa Neuroscience Institute; Immunology; Internal Medicine
Record Identifier: 9984065480002771

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