Motor impairment in Alzheimer's disease and transgenic Alzheimer's disease mouse models

In this commentary, we accent the accumulating evidence for motor impairment as a common feature of early Alzheimer's disease (AD) pathology. In addition, we summarize the state of knowledge on this phenotype in experimental mouse models, expressing AD-associated genes like tau or amyloid precursor protein.     

雌激素与阿尔采末病

阿尔采末病（ＡＤ）是一种慢性的大脑神经退行性变性疾病,主要表现为进行性远近记忆力障碍、语言、情感、认知、行为等方面改变。近年研究发现,ＡＤ的发病与雌激素缺乏有密切关系。雌激素可通过多种途径、环节延缓ＡＤ发生、发展。如促进可溶性β－淀粉样蛋白（Ａβ）生成,维持中枢神经元组织结构,影响中枢神经递质含量、酶活性、载脂蛋白Ｅ（ａｐｏＥ）生成及抗氧化等。目前,雌激素作为预防和治疗ＡＤ的药物日益受到重视,可望     

同型半胱氨酸与阿尔采末病

阿尔采末病 (AD)是多因素共同作用的危害公众健康的复杂疾病 ,是神经科学工作者关注的焦点。近年来 ,有报道显示 ,血浆中同型半胱氨酸 (Hcy)的浓度与AD有密切联系。本文就血浆中Hcy的浓度与AD发生、发展的联系、可能的作用机制 ,以及两者联系的应用前景作一简述     

Therapy for Alzheimer's disease

Therapeutic strategies aimed to treat Alzheimer's disease (AD) may either produce an attenuation of symptoms or slowdown deterioration by attenuating progression of the disease. Presently, cholinesterase inhibitors (ChEI) have shown the most promising therapeutic effects. The best documented clinical efficacy of ChEI are studies of THA (tacrine, tetrahydroaminoacridine). The results of five recent studies in a total of 1,242 patients are discussed. Based on differences from placebo in scoring, a gain of 2–12 (MMSE) or 5–6 (ADAS) in deterioration can be seen for a THA treatment of 2–3 mo duration. This suggests that if treatment with THA will be extended to a longer period, the drug effect may not be only a symptomatic improvement but also a slowdown of disease course. A similarity of THA's effect in AD withl-deprenyl effects in Parkinson's is suggested.     

Ammonia and Alzheimer's disease

Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder. Behavioural, cognitive and memory dysfunctions are characteristic symptoms of AD. The formation of amyloid plaques is currently considered as the key event of AD. Other histological hallmarks of the disease are the formation of fibrillary tangles, astrocytosis, and loss of certain neuronal systems in cortical areas of the brain. A great number of possible aetiologic and pathogenetic factors of AD have been published in the course of the last two decades. Among the toxic factors, which have been considered to contribute to the symptoms and progression of AD, ammonia deserves special interest for the following reasons: (a) Ammonia is formed in nearly all tissues and organs of the vertebrate organism; it is the most common endogenous neurotoxic compounds. Its effects on glutamatergic and GABAergic neuronal systems, the two prevailing neuronal systems of the cortical structures, are known for many years. (b) The impairment of ammonia detoxification invariably leads to severe pathology. Several symptoms and histologic aberrations of hepatic encephalopathy (HE), of which ammonia has been recognised as a pathogenetic factor, resemble those of AD. (c) The excessive formation of ammonia in the brains of AD patients has been demonstrated, and it has been shown that some AD patients exhibit elevated blood ammonia concentrations. (d) There is evidence for the involvement of aberrant lysosomal processing of beta-amyloid precursor protein (beta-APP) in the formation of amyloid deposits. Ammonia is the most important natural modulator of lysosomal protein processing. (e) Inflammatory processes and activation of microglia are widely believed to be implicated in the pathology of AD. Ammonia is able to affect the characteristic functions of microglia, such as endocytosis, and cytokine production. Based on these facts, an ammonia hypothesis of AD has first been suggested in 1993. In the present review old and new observations are discussed, which are in support of the notion that ammonia is a factor able to produce symptoms of AD and to affect the progression of the disease.     

小胶质细胞与阿尔茨海默病

国内外对阿尔茨海默病（Alzheimer’s disease,AD）神经元病理和神经胶质细胞病理机制进行了大量探索,小胶质细胞（microglia,MG）是中枢神经系统的免疫细胞,在致炎因素作用下它被激活成反应性MG,反应性MG既具有保护神经元的作用,也能分泌细胞毒因子、补体蛋白而损害神经元。尽管目前AD发病机理还不清楚,但大多数学者认为β淀粉样蛋白（Aβ）沉积激活MG引起的炎症反应是AD的核心病理机制。     

Copper and Alzheimer's disease

Copper is essential for some of the enzymes that have a role in brain metabolism. Sophisticated mechanisms balance copper import and export to ensure proper nutrient levels (homeostasis) while minimizing toxic effects. Several neurodegenerative diseases including Alzheimer's disease (AD) are characterized by modified copper homeostasis. This change seems to contribute either directly or indirectly to increased oxidative stress, an important factor in neuronal toxicity. When coupled to misfolded proteins, this modified copper homeostasis appears to be an important factor in the pathological progression of AD.