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

这个项目的目的，就像整个建议一样，是 测试研究神经组织异常的价值， 通过测试这些异常之间的关系， 与临床综合征或其亚组的关系。 临床上，DAT患者、患有其他疾病（疾病 对照组），配偶和其他无关的认知完整的受试者， 将广泛检查年龄和性别相当的（完整对照） 通过一个成熟的临床痴呆症服务。 所有，包括完整的 对照组将接受神经心理学测试。 一切都会，如果 可能的话，会进行尸检。 皮肤细胞的培养将受到严格控制， 包括活检部位和与培养物中生物学年龄相关的参数 （累积群体倍增水平[cPDL]和完成的寿命%）， 为了确保DAT和对照细胞在可比较的条件下进行研究， 条件 在电池中测量的参数将包括两个相关参数， 在DAT大脑中积累的物质。 淀粉样前体蛋白 (APP)将在mRNA和蛋白质（免疫化学） 程度. 与成对螺旋抗体反应的材料 纤维（PHF）将进行免疫细胞化学研究，使用 半定量技术和培养条件，PI和 同事们已经发现导致抗PHF反应性物质的表达， 培养的DAT细胞中，并在很小程度上从控制细胞。 （项目2旨在开发定量免疫化学技术， 测量抗P HF反应材料，然后将其应用于 这些细胞）。在培养的细胞中测量的其他参数将是 至少有两个实验室（包括本单位）发现 培养的DAT细胞异常：异丙肾上腺素刺激的环磷酸腺苷 合成，细胞钙稳态，氧化 [U-14 C]谷氨酰胺。 数据将存储在关系数据库（SIR软件）中， 培养细胞异常与临床的关系 DAT或其亚型综合征的详细统计分析 一个统计顾问。 在未来的研究中，任何异常的诊断效用， 发现与疾病有关的培养细胞将被 测试，包括他们是否似乎是特质或状态依赖 标记。

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.