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Magnetic resonance spectroscopic analysis of Alzheimer mouse brain that express mutant human APP shows altered neurochemical profile

, : Magnetic resonance spectroscopic analysis of Alzheimer mouse brain that express mutant human APP shows altered neurochemical profile. Society for Neuroscience Abstract Viewer & Itinerary Planner : Abstract No 203 10

Introduction-Transgenic mice that express mutant human amyloid precursor protein (APPTg2576) develop beta-amyloid (Abeta) plaques throughout the cortex starting at 10-12 months of age. We examined the neurochemical profile of APPTg2576 brain using in vitro and in vivo magnetic resonance spectroscopy, gross abnormalities using magnetic resonance imaging, plaque distribution, size and number using immunohistochemistry.Methods-Transgenic mice and wild type controls were anesthesized with halothane and scanned at 4.7T using T2-weighted imaging (TR/TE = 3.3/60 ms). Spectroscopy was run using a PRESS sequence with multiple TE values. Brains were cut into liquid nitrogen and dissected and extracted with PCA. Then in vitro spectra (500MHz) were run on the tissue samples for APP and wild-type mice. Mice were perfused and brains were collected and and cut for immunohistochemistry. Serial sections were analyzed using Image-Pro Plus version 4.5.Results-We found that taurine, scyllo-inositol are increased (49 and 73% respectively), and aspartate (-67%), NAA (-26%), glutamate (-40%) are decreased in the cerebral cortex of APP transgenic mice at 18 months of age when Abeta deposits are wide spread. T2 images of the brains suggests increased ventricular size.Discussion-Increased brain levels of taurine and decreased NAA are consistent with decreased healthy neuron and increased glia, and are similar to findings of decreased NAA and increased myo-inositol in human AD brains. Correlation between the severity of Abeta deposition and altered neurochemical profile remains to be studied. Nevertheless, the altered neurochemical profile may be a marker to test therapeutics in this mouse model.


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