Journal article
Staging of Neurofibrillary Degeneration Caused by Human Tau Overexpression in a Unique Cellular Model of Human Tauopathy
The American journal of pathology, Vol.158(1), pp.235-246
01/2001
DOI: 10.1016/S0002-9440(10)63962-4
PMCID: PMC1850256
PMID: 11141497
Abstract
The hyperphosphorylation of human tau and its aggregation into neurofibrillary tangles are central pathogenic events in familial tauopathies and Alzheimer’s disease. However, the cellular consequences of neurofibrillary tangle formation
in vivo
have not been directly studied because cellular models of human neurofibrillary degeneration have been unavailable until recently. Incorporation of human tau into filaments
in vivo
and the association of filamentous tau with cytodegeneration were first demonstrated experimentally with the overexpression of human tau in identified neurons (anterior bulbar cells) in the lamprey central nervous system. In this system, filamentous tau deposits are associated with the loss of dendritic microtubules and synapses, plasma membrane degeneration, and eventually the formation of extracellular tau deposits and cell death. Here we show that human tau hyperphosphorylation in anterior bulbar cells is spatiotemporally correlated with a highly stereotyped sequence of degenerative stages closely resembling those seen in human neurofibrillary degeneration. Hyperphosphorylated tau deposits first appear in the distal dendrites and somata, together with degenerative changes that begin in distal dendrites and progress proximally over time. This sequence is independent of the tau isoform used, the presence of epitope tags and the method used to overexpress tau, and thus has important implications for the cytopathogenesis of human neurofibrillary disease.
Details
- Title: Subtitle
- Staging of Neurofibrillary Degeneration Caused by Human Tau Overexpression in a Unique Cellular Model of Human Tauopathy
- Creators
- Garth F Hall - University of Massachusetts, Lowell, Massachusetts; the Department of Pathology and Laboratory MedicineVirginia M.-Y Lee - University of Pennsylvania, Philadelphia, Pennsylvania; and the Department of Internal MedicineGloria Lee - University of Iowa, Iowa City, IowaJun Yao - University of Massachusetts, Lowell, Massachusetts; the Department of Pathology and Laboratory Medicine
- Resource Type
- Journal article
- Publication Details
- The American journal of pathology, Vol.158(1), pp.235-246
- Publisher
- American Society for Investigative Pathology
- DOI
- 10.1016/S0002-9440(10)63962-4
- PMID
- 11141497
- PMCID
- PMC1850256
- ISSN
- 0002-9440
- eISSN
- 1525-2191
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: AG13909
- Language
- English
- Date published
- 01/2001
- Academic Unit
- Iowa Neuroscience Institute; Immunology; Internal Medicine
- Record Identifier
- 9984065485802771
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