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阿尔茨海默病与老年痴呆症:生化特征及治疗方面

Alzheimer's disease and senile dementia: biochemical characteristics and aspects of treatment.

作者信息

Gottfries C G

出版信息

Psychopharmacology (Berl). 1985;86(3):245-52. doi: 10.1007/BF00432208.

DOI:10.1007/BF00432208
PMID:2863836
Abstract

Alzheimer's disease (AD) and senile dementia (SD) are often classified together, but there are genetic, biochemical, neuropathological and clinical arguments for separating them. The well-known Alzheimer lesions in the brains of patients with AD and SD are described, as is the loss of neurons in the locus coeruleus. White matter changes in brains from patients with dementia are discussed and related to AD and SD. Biochemical changes in brains of patients with AD and SD include reduced activity of acetylcholinesterase (AChE) and choline-acetyltransferase (CAT), indicating reduced activity in the acetylcholinergic system. There is also, however, reduced activity in the dopamine (DA), noradrenaline (NA) and 5-hydroxytryptamine (5-HT) system. The active amines are decreased while the end metabolites are decreased to a lesser extent or normal. The levels of the active amines are thought to reflect the number of neurons, while the levels of end metabolites reflect the rate of turnover in the system. 3-Methoxy-4-hydroxyphenylglycol (MHPG) is increased to levels above normal, which may indicate an increased rate of turnover in the NA system. Monoamine oxidase B (MAO-B), which is increased in advanced age, is further increased in patients with AD and SD. It is assumed that this enzyme is localized in extraneuronal tissue, and therefore the increase may reflect a gliosis. In brains from patients with AD and SD neuropeptides are also studied. Only somatostatin and substance P, however, seem to be reduced, indicating selective damage to the neuropeptides. The biochemical changes can be given pathogenetic importance.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

阿尔茨海默病(AD)和老年痴呆症(SD)常被归为一类,但从遗传学、生物化学、神经病理学和临床角度来看,有理由将它们区分开来。文中描述了AD和SD患者大脑中著名的阿尔茨海默病变,以及蓝斑核中神经元的丧失。探讨了痴呆症患者大脑中的白质变化及其与AD和SD的关系。AD和SD患者大脑的生物化学变化包括乙酰胆碱酯酶(AChE)和胆碱乙酰转移酶(CAT)活性降低,表明乙酰胆碱能系统活性降低。然而,多巴胺(DA)、去甲肾上腺素(NA)和5-羟色胺(5-HT)系统的活性也降低。活性胺减少,而终末代谢产物减少程度较小或正常。活性胺的水平被认为反映神经元数量,而终末代谢产物的水平反映系统中的周转速率。3-甲氧基-4-羟基苯乙二醇(MHPG)升高至正常水平以上,这可能表明NA系统周转速率增加。单胺氧化酶B(MAO-B)在老年时升高,在AD和SD患者中进一步升高。据推测,这种酶定位于神经外组织,因此其升高可能反映了胶质增生。在AD和SD患者的大脑中也研究了神经肽。然而,似乎只有生长抑素和P物质减少,表明神经肽受到选择性损伤。这些生物化学变化具有致病重要性。(摘要截短至250字)

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