Study On Imaging And Pathology Of AD Animal Model

Alzheimer's Disease (AD) , a general type of dementia with a high incidence in China, influences the life of elders seriously and gains much more regard nowadays. AD is a progressive neurodegenerative disease characterized by the impairment of cognitive functions and by beta amyloid plaques in the cerebral cortex and the hippocampus. The clinical identification and differential diagnosis of AD is especially challenging in the early stages, but the need for early, accurate diagnosis has become more important, now that several medications for the treatment of mild to moderate Alzheimer's disease (AD) are available. Though the clinical researches prove the diagnostic value of imaging examination, it lacks of confirmation by pathology and pathophisiology, obstructing the deeply discussion of the results from these researches. What's more, studing on patients with symptoms makes it not able to reveal the abnormity in early stage. Working on the animal model of AD is a preferred substitute. To this day, there is no report about MRI volumetric analysis and MRS study on AD mouse model, neither does the study on pathologic and pathophisiologic basis of these image and lH MRS changes except the senile plaque.The purpose of this study was to fist investigate the image changes early in disease progression, even in the preclinical stage, and make sure the diagnosticvalue of MRI, MRI volumetric analysis and 1H MRS, second search for basic mechanism of these image alternatives.The research employed the animal model induced by AB (1-40) injected into hippocampal, and the control ones were injected with the vehicle. All of the model and control were divided randomly into 5 groups , 18 mouse in each group, and the examinations were taken on these groups at different time points: 1, 2, 4, 6 and 8 weeks after injection. The items consisted of: 1. The head MRI and hippocample MRI volumetric analysis. 2. The in vitro 1H MRS taken out by 9.4T NMR, evaluating the level of NAA, MI, Cho and Cr. 3. Behavioral examination, including short-term memory, long-term memory and learning ability. 4. Neural pathologic examination including HE, Congo red , Bielschowsky pigmentation and also the electron microscope. 5. Pathophisiological examination testing ATPase, AchE and TO AC.Neural pathologic examination confirmed the success of AD mouse model. The model manifested the neural fibril degeneration and tangles from 2 weeks after the treatement, while the senile plaque had not come into being since 6 weeks after injection. The hyperplasia of microglia was obvious without concomitance of the absence of neuron.Pathophisiological results were that, compared with the control group, the level of ATPase, AchE and TAOC fall markedly. The changes in Ca2+-Mg2+-ATPase and TAOC within the model group had statistic sense. There was correlativity between TAOC and Na+-K+-ATPase activity (Pearson correlation is 0.405, P < 0.05 ).Behavioral examination revealed that shot-term and long-term memory of mouse model reduced at 1-week point. While at 8-week point, long-term memory and learning ability decreased distinctly. There were correlativitybetween long-term memory and AchE activity, so did the learning ability and TAOC(Pearson correlation is 0.384 and 0.579, p value is 0.036 and 0.001, respectively).The brain MRI of mouse show the blurring of hippocample boundary in the early stage, then came the low signal intensity on T2WI with different size and shape in hippocampus and parenchyma nearby. The configuration of hippocampus became irregular, together with the dilatation of ventricle and subarachnoid space round temporal pole. The MRI volumetric analysis of hippocampus did not show any abnormity.The in vitro 1H MRS of hippocampus revealed the variety of NAA/Cr, which had statistic sense compared with the control ones. The level of NAA/Cr decreased in the first month and then increased, which course had negative correlativity with TAOC(Pearson correlation was -0.624, p value was 0.003) and positive correlativity with Cho/Cr level(Pearson correlatio...