GERIATRIC DEMENTIA RESEARCH CLINIC

老年痴呆症研究诊所将继续整合 对病人、大脑和神经组织的研究， 阿尔茨海默病和其他痴呆症。 总体假设 正在测试的是，在一个重要的患者亚组中， 阿尔茨海默病是一种遗传性疾病， 可以在非神经组织中有效研究的表现 以及大脑。 核心将继续精心供应 评估患者和研究组织，包括尸检大脑; 它还将提供活组织检查大脑（“神经外科废物”）、组织 培养物（包括来自大激酶的细胞）、抗体，以及 统计、计算机和行政支持。 代谢 研究将定义已经记录的异常， 细胞内钙稳态与细胞生理 使用新的荧光分光光度法， 技术. 已证实的细胞缺陷部位 氧化代谢将用放射化学和 其他探头，包括氧电极测量。 分子生物学研究将测试这些缺陷是否 焦磷酸硫胺素（TPP）依赖酶证明， 在阿尔茨海默氏症大脑中反映出结构异常， 转录的各个基因，至少在层 患者 免疫细胞化学和原位杂交研究 将测试N.基底核 阿尔茨海默氏病中的细胞可能与其表现出的 相对富集至少一种缺陷TPP- 依赖酶 先导性治疗试验将测试 我们的实验表明， 研究：3，4-二氨基吡啶和高剂量硫胺素。 (The后者 导致了统计学上尽管没有临床意义的 这些患者认知能力的改善， 研究）。

The Geriatric Dementia Research Clinic will continue integrated studies of patients, of brain, and of extranueral tissues, in Alzheimer disease and other dementias. The overall hypothesis being tested is that in a significant subgroup of patients, Alzheimer's disease is a genetic disorder with systemic manifestations which can usefully be studied in non-neural tissues as well as in brain. The core will continue to supply meticulously evaluated patients and tissues for study, including autopsy brain; it will also provide biopsy brain ("neurosurgical waste"), tissue cultures (including cells from large kindreds), antibodies, and statistical, computer, and administrative support. Metabolic studies will define the already documented abnormalities in cellular calcium homeostasis in relation to cell physiological events over msec to min, using new spectrofluorometric technology. The site(s) of demonstrated deficiencies in cellular oxidative metabolism will be defined with radiochemical and other probes, including oxygen electrode measurements. Molecular biological studies will test whether the deficiencies in thiamine pyrophosphate (TPP) dependent enzymes demonstrated in Alzheimer brain reflect abnormalities in structure or transcription of the respective genes, at least in strata of patients. Immunocytochemical and in situ hybridization studies will test the possibility that selective vulnerability of n. basalis cells in Alzheimer's disease may relate to their demonstrated relative enrichment in at least one of the deficient TPP- dependent enzymes. Pilot therapeutic trials will test the value in Alzheimer's disease of agents suggested by our experimental studies: 3,4-diaminopyridine and high dose thiamine. (The latter led to a statistically although not clinically significant improvement in cognition in these patients in a preliminary study).