MICROTUBULE PROTEINS IN ALZHEIMER'S DISEASE

微管相关蛋白(MAPs)、tau和MAP1B 在正常的神经元发育过程中受到调节。证据在不断积累 提示胎儿特征在脆弱的神经元中重新出现 参与阿尔茨海默病(AD)的病理研究。胎儿和成体都有 已知是成对螺旋细丝的组成部分 (PHF)和初步证据表明，受Ad影响的神经元表达 高水平的MAP1B。因此，我们建议确定相对的 这两种蛋白质在脑区的含量，并确定 阿尔茨海默病和对照组大脑中胎儿/成人tau的比率。研究将继续进行 评估AD与对照tau和AD蛋白A68的性质。非- 微管蛋白tau相互作用蛋白(TIPS)，以及新发现的200 kDa tau蛋白。 类似的多肽将在AD和对照脑中被检测和定量. 将使用AD和正常可溶性进行微管结合研究 Tau和A68，以确定这些属性在 疾病状态。此外，AD神经元的代谢能力 改变的tau将通过体外蛋白酶实验进行评估， AD和对照CSF中的tau量将被确定。成功 这些实验的完成将有助于建立 哪个tau、MAP1B和200 kDa多肽在它们的 AD病理中的表达、形式或相互作用。

The microtubule-associated proteins (MAPs), tau and MAP1B are highly regulated during normal neuronal development. Evidence is accumulating suggesting the re-emergence of fetal characteristics in vulnerable neurons involved in Alzheimer's Disease (AD) pathology. Both fetal and adult forms of tau are known to be integral components of the paired helical filament (PHF) and preliminary evidence indicates that Ad-affected neurons express high levels of MAP1B. Therefore, we propose to determine the relative amounts of both of these proteins in brain regions and to determine the fetal/adult tau ratios in AD and control brains. Studies will continue to asses the properties of AD vs control tau and the AD protein, A68. Non- tubulin tau interacting proteins (TIPs), and a newly described 200 kDa tau- like polypeptide will be and quantified in AD and control brain. Microtubule binding studies will be performed using AD and normal soluble tau as well as A68 to ascertain whether these properties are altered in the disease state. In addition, the ability of the AD neuron to metabolize altered tau will be assessed by in vitro protease experiments and the amounts of tau in AD and control CSFs will be determined. Successful completion of these experiments will aid in establishing the degree to which tau, MAP1B and the 200 kDa polypeptide are altered in either their expression, form or interactions in AD pathology.