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Alzheimer's disease-like tau neuropathology leads to memory deficits and loss of functional synapses in a novel mutated tau transgenic mouse without any motor deficits.
- Source :
-
The American journal of pathology [Am J Pathol] 2006 Aug; Vol. 169 (2), pp. 599-616. - Publication Year :
- 2006
-
Abstract
- Tau transgenic mice are valuable models to investigate the role of tau protein in Alzheimer's disease and other tauopathies. However, motor dysfunction and dystonic posture interfering with behavioral testing are the most common undesirable effects of tau transgenic mice. Therefore, we have generated a novel mouse model (THY-Tau22) that expresses human 4-repeat tau mutated at sites G272V and P301S under a Thy1.2-promotor, displaying tau pathology in the absence of any motor dysfunction. THY-Tau22 shows hyperphosphorylation of tau on several Alzheimer's disease-relevant tau epitopes (AT8, AT100, AT180, AT270, 12E8, tau-pSer396, and AP422), neurofibrillary tangle-like inclusions (Gallyas and MC1-positive) with rare ghost tangles and PHF-like filaments, as well as mild astrogliosis. These mice also display deficits in hippocampal synaptic transmission and impaired behavior characterized by increased anxiety, delayed learning from 3 months, and reduced spatial memory at 10 months. There are no signs of motor deficits or changes in motor activity at any age investigated. This mouse model therefore displays the main features of tau pathology and several of the pathophysiological disturbances observed during neurofibrillary degeneration. This model will serve as an experimental tool in future studies to investigate mechanisms underlying cognitive deficits during pathogenic tau aggregation.
- Subjects :
- Aging
Animals
Behavior, Animal
Disease Models, Animal
Gliosis pathology
Hippocampus cytology
Hippocampus pathology
Hippocampus ultrastructure
Humans
Mice
Mice, Transgenic
Nerve Degeneration
Neurofibrillary Tangles ultrastructure
Phosphorylation
Protein Conformation
Synaptic Transmission physiology
tau Proteins chemistry
tau Proteins metabolism
Alzheimer Disease pathology
Memory Disorders pathology
Motor Skills Disorders pathology
Mutation genetics
Synapses pathology
tau Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0002-9440
- Volume :
- 169
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The American journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 16877359
- Full Text :
- https://doi.org/10.2353/ajpath.2006.060002