Neuroscience 2005 Abstract
| Presentation Number: | 208.10 |
|---|---|
| Abstract Title: | Imaging neurofibrillary pathology in the living mouse brain. |
| Authors: |
Spires, T. L.*1
; Pitstick, R.2
; Carlson, G. A.2
; Ashe, K. H.3
; Hyman, B. T.1
1MassGeneral Inst. for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, MA 2MT, 114 16th St, 02129, 3USA, 114 16th St, 02129, |
| Primary Theme and Topics |
Disorders of the Nervous System - Neurodegenerative and Movement Disorders -- Dementia: Tau |
| Session: |
208. Tau and Tau Kinases II Poster |
| Presentation Time: | Sunday, November 13, 2005 9:00 AM-10:00 AM |
| Location: | Washington Convention Center - Hall A-C, Board # RR43 |
| Keywords: | tau, Alzheimer, multiphoton |
Accumulation of hyperphosphorylated tau protein into neurofibrillary tangles (NFT) in Alzheimer disease and other tauopathies correlates with neuron loss and cognitive decline; but the relationship of NFT to neuron dysfunction and death in neurodegenerative diseases remains unclear. Recently, a regulatable transgenic mouse line was developed (rTg4510) that expresses human tau with the tauopathy-associated P301L mutation, which can be suppressed with doxycycline. These mice develop progressive behavioral deficits, neuron loss, and tangle formation that can be prevented by transgene suppression (SantaCruz et al., 2005, submitted; Orne et al, sfn 2005 poster). In this study cortical neurons of rTg4510 and control mice were infected with adeno-associated virus carrying the gene for enhanced green fluorescent protein and in vivo multiphoton microscopy was used to investigate neuron morphology and tangles in the living brain. We observe thioflavine S positive neurons similar to staining of NFT in human tauopathy cases. Neuronal nuclei, stained with DAPI, appear morphologically normal despite extensive neuron death occurring at this age in the cortex. While many GFP-filled neuronal processes appear morphologically normal, we observe some remarkably tortuous neurites. This study demonstrates for the first time the ability to observe neurofibrillary pathology in the live brain, and indicates that neurons in rTg4510 mice may become morphologically abnormal before dying.
Supported by NIH AG26249, AG08487, AG00277, Alzheimer Association Pioneer Award
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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