CLIN.SIGN. OF ABNOR. IN CELLS CULT. FROM PAT. WITH ALZHEIMER DISEASE

这个项目的目的，就像整个提案的目的一样，是为了 探讨神经外组织异常的研究价值 通过测试这些异常与阿尔茨海默病(DAT)患者的关系 归于临床综合征或其亚组。 临床上，DAT患者、其他疾病患者(疾病 控制)，以及配偶和其他不相关的认知完整的受试者 将对可比的年龄和性别(完整的对照)进行广泛检查 通过已建立的临床痴呆症服务。全部，包括完好无损 对照组，将接受神经心理测试。所有人都会的，如果 有可能，会被追踪到尸检。 皮肤细胞的培养将受到严格控制， 包括活检部位和培养中与生物学年龄有关的参数 (累计人口倍增水平[CPDL]和完成的寿命百分比)， 确保在可比较的情况下研究DAT和控制单元 条件。 在单元格中测量的参数将包括两个与 积聚在DAT脑中的物质。淀粉样前体蛋白 (APP)将在mRNA和蛋白质(免疫化学)两个方面进行研究 级别。与成对螺旋抗体发生反应的材料 细丝(PHF)将用免疫细胞化学方法研究，使用 半定量技术和培养条件 同事们发现导致抗PHF活性物质在 培养的DAT细胞，在对照组细胞中的程度要小得多。 (项目2旨在开发定量免疫化学技术以 测量抗P-HF反应材料，然后将其应用于 这些细胞。)在培养细胞中测量的其他参数将是 由至少两个实验室(包括本单位)发现的 培养的DAT细胞异常：异丙肾上腺素刺激的环磷酸腺苷 合成、细胞内钙稳态和氧化 [U-14C]谷氨酰胺。 数据将存储在关系数据库(SIR软件)中，以及 培养细胞异常与临床的关系 DAT证候及其亚型的详细统计分析 和一位统计顾问。 在未来的研究中，任何异常在诊断中的作用 被发现与这种疾病有关的培养细胞将是 测试，包括他们是否看起来与特质或状态有关 记号笔。

The aim of this project, like that of the overall proposal, is to test the value of studying abnormalities in extraneural tissues from Alzheimer (DAT) patients by testing the relation of these abnormalities to the clinical syndrome or its subgroups. Clinically, DAT patients, patients with other disorders (disease controls), and spousal and other unrelated cognitively intact subjects of comparable age and sex (intact controls) will be extensively examined through an established clinical dementia service. All, including intact controls, will receive neuropsychological testing. All will, if possible, be followed up to autopsy. Cultures of cells from skin will be meticulously controlled, including biopsy site and parameters related to biological age in culture (cumulative population doubling level [cPDL] and % life-span completed), to ensure that DAT and control cells are studied under comparable conditions. Parameters measured in the cells will include two related to materials which accumulate in DAT brain. The amyloid precursor protein (APP) will be studied at both the mRNA and protein (immunochemical) levels. Materials which react with antibodies to paired helical filaments (PHF) will be studied immunocytochemically, using semiquantitative techniques, and culture conditions which the PI and coworkers have found lead to expression of anti-PHF reactive materials in cultured DAT cells and to a much lesser degree in cells from controls. (Project 2 aims to develop quantitative immunochemical techniques to measure anti-P HF reactive materials, which would then be applied to these cells.) Other parameters measured in the cultured cells will be those found by at least two laboratories (including this unit) to be abnormal in cultured DAT cells: isoproterenol-stimulated cyclic AMP synthesis, cellular calcium homeostasis, and oxidation of [U-14C]glutamine. Data will be stored in a relational data base (SIR software), and the relations of the abnormalities in the cultured cells to the clinical syndrome of DAT or its subtypes tested by detailed statistical analysis with a statistical consultant. In future studies, the diagnostic utility of any abnormalities in the cultured cells which are found to relate to the disease will be tested, including whether they appear to be trait- or state-dependent markers.