ENDOCRINE CALCIUM/PHOSPHATE REGULATION, BRAIN METABOLISM, AND ALZHEIMER'S DISEASE

这个项目的目的是验证这样一种假设，即钙的变化 调节激素和血清钙/磷(Ca/PO4)动态平衡 与阿尔茨海默病的病因/发病机制直接相关 人类。血清Ca/PO4调节改变对大脑的影响 通过长期改变的大脑PO4/Ca动态平衡，通过直接 外周激素作用模式改变对脑神经元的影响 (含有维生素D、降钙素、糖皮质激素和甲状旁腺激素 激素(PTH)受体，或者它们可能通过衰老相关的变化而发生 在脑神经元水平上的钙调节或激素敏感性。 在这方面，一个有趣的途径涉及到这样一种可能性 大脑能量代谢可能会改变，可能是由于慢性 亚临床低磷血症和由此导致的缺氧，进而可能 导致钙缓冲功能受损和脑细胞丢失。 该项目的实验目标数量较少，相对较多。 直截了当。然而，每一次都将非常耗时。这些 目标是： 1)前瞻性研究AD最早期阶段的受试者 将测试外周钙调节、内分泌的纵向研究 功能和脑能量代谢，并将这些与发病和 AD的进展超过两年。将对以下各项进行测量 四种主要钙调节激素(维生素)的反应性和有效性 D代谢物、肾上腺-垂体激素、甲状旁腺素和降钙素)的关系 神经心理测试和磁共振测试(MRI)。 2)对被诊断为 根据NIA-NINDS标准，使用钙调节激素治疗，可能为AD 被认为对慢性人类足够安全的(1，25(OH)2-D) 实验。治疗将为期两年，评估将是 通过神经心理测试和核磁共振检查。 即使这些研究的部分结果是积极的，也将具有巨大的潜力 提供新的治疗方法和新的早期诊断方法 阿尔茨海默氏症。

This project is aimed at testing the hypothesis that alterations in calcium regulatory hormones and serum calcium/phosphate (Ca/PO4) homeostasis, are directly related to the etiology/pathogenesis of Alzheimer's Disease in humans. The effects of altered serum Ca/PO4 regulation on the brain could occur through chronically altered brain PO4/Ca homeostasis, through direct impact of altered peripheral hormonal patterns of actions on brain neurons (which contain vitamin D, calcitonin, glucocorticoid, and parathyroid hormone (PTH) receptors, or they may occur through aging-associated changes in Ca regulation or hormonal sensitivity at the level of the brain neuron. One interesting pathway in this context, involves the possibility that cerebral energy metabolism may be altered, possibly due to chronic subclinical hypophosphatemia and resulting hypoxia, which in turn could result in impaired Ca buffering and brain cell loss. The experimental goals of this project are few in number and relatively straightforward. However, each will be extremely time-consuming. These are to: 1) Study subjects in the very earliest stages of AD in a prospective longitudinal study that will test peripheral Ca regulation, endocrine function and cerebral energy metabolism and relate these to the onset and progression of AD over two years. Measurements will be made of the responsiveness and efficacy of four major Ca regulatory hormones (Vitamin D metabolites, adrenal-pituitary hormones, PTH and calcitonin) in relation to neuropsychological tests and magnetic resonance tests (MRI). 2) Conduct an experimental intervention test in humans diagnosed with probable AD by NIA-NINDS criteria, using a Ca regulatory hormonal treatment (1,25(OH)2-D) that is considered sufficiently safe for chronic human experimentation. Treatment would be for two years, and assessment would be by neuropsychological tests and MRI. Even partly positive results of these studies would hold major potential for both new therapeutic and new early diagnostic approaches to the problem of Alzheimer's disease.