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Trojanowski Laboratory

Summary:

Research currently centers on molecular mechanisms of neuron dysfunction, degeneration and death in normal aging and in neurodegenerative diseases (Alzheimer's and Parkinson's disease, frontotemporal dementias with/without parkinsonism, motor neuron disease, etc.). This research uses immunological, biochemical, genetic, molecular and morphological methods to study human CNS and PNS tissue samples (postmortem or surgical), cell lines, synthetic proteins, and transgenic models of neurodegenerative diseases. Dr. Trojanowski is involved in collaborative initiatives between PENN Medicine and the University of Pennsylvania School of Nursing to advance drug discovery, clinical research, and patient care related to Alzheimer’s disease and the Alzheimer's Disease Neuroimaging Initiative (ADNI) to test whether serial magnetic resonance imaging, positron emission tomography, other biological markers, and clinical and neuropsychological assessment can be combined to measure the progression of mild cognitive impairment (MCI) and early Alzheimer's disease.

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Organisms and Viruses

  • B6;C3-Tg(Prnp-MAPT*P301S)PS19Vle/J ( Mus musculus )

    "These PS19 transgenic mice (P301S Tg mice) express the P301S mutant form of human microtubule-associated protein tau (MAPT), under the direction of the mouse prion protein, Prnp, promoter. The expression of the mutant human MAPT is five-fold higher than the expression of the endogenous mouse MAPT protein. Hyperphosphorylated, insoluble mutant human MAPT protein in the brain accumulates with age causing decreased microtubule binding. At three months of age, transgenic mice exhibit clasping and limb retraction when lifted by the tail, which progresses to limb weakness. By 10 months of age the mice exhibit a hunched back and paralysis, followed by inability to feed. Transgenic mice have a median lifespan of approximately nine months with approximately 80% dying by 12 months. Histological analysis reveals neuron degeneration in hippocampus and ventricular dilatation (brain atrophy) by eight months of age, although significant neuron degeneration in the hippocampus occurs at approximately nine months of age. Neuron loss spreads to the amygdala, neocortex and entorhinal cortex by 12 months of age. Defective translocation of endoplasmic reticulum proteins in affected neurons is observed as early as three months of age. The onset of neurofibrillay tangle formation in the neocortex, amygdala, hippocampus, brain stem and spinal cord is five months of age. Transgenic mice display neuroinflammation with microglial activation and astrogliosis. The ultrastructure of the neurofibrillay tangle-like lesions detected is similar to that found in brain lesions of human Alzheimer's disease and tauopathy patients. Degradation of synaptic function is significant by six months of age. These mice cannot be bred to homozygosity as homozygous females do not mate."


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Last updated: 2014-04-16T09:25:05.935-04:00

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The eagle-i Consortium is supported by NIH Grant #5U24RR029825-02 / Copyright 2016