《生命科学》 2013, 25(2): 184-190
摘 要：摘 要：阿尔茨海默病(Alzheimer’s disease， AD) 主要表现为认知能力下降，进行性记忆丧失，性格改变，语言功能障碍，最终发展为痴呆。AD 的主要神经病理学表现为：沉积在细胞外的淀粉样蛋白斑；细胞内的神经纤维缠结；基底前脑胆碱能神经元死亡。氧化应激、线粒体损伤和代谢能力降低是AD 的重要病理生理学机制。实验性维生素B1 缺乏(thiamine deficiency， TD) 是研究脑代谢降低引起神经元死亡的经典动物模型。TD 降低脑内维生素B1 依赖性代谢酶活性，导致氧化代谢异常、丘脑核团神经元特异性死亡、胶质细胞激活、炎症反应等神经退行性疾病类似的病理改变。以TD 为模型的研究显示，代谢紊乱、氧化应激、内质网应激、蛋白质折叠异常和炎症反应是神经元死亡和β 淀粉样蛋白聚集的重要机制。增加体内可利用的维生素B1 可改善老年性痴呆模型动物的认知水平，减轻脑病理改变。这些结果提示，补充维生素B1 可能是延缓老年性痴呆发展的一种有效方法。
关键词：阿尔茨海默病；β- 淀粉样蛋白聚集；神经元死亡；代谢紊乱；维生素B1 缺乏
Abstract: Abstract: Alzheimer’s disease (AD) is the most common cause of dementia in the elderly population. The clinical and pathological features of AD are progressive cognitive decline， memory loss， personality changes， language dysfunction， and ultimately dementia. The major neuropathological hallmarks of AD are selective loss of cholinergic neuron in basal forebrain， accumulation of amyloid plaques in the cortex， and neurofibrillary tangles. Mitochondrial dysfunction， oxidative stress and diminished metabolism are the major pathophysiological features of AD. Experimental thiamine deficiency (TD) is a classic model for exploring the molecular mechanisms of selective loss of neuron in neurodegenerative diseases. Studies have shown TD produces a time-dependent selective neuronal loss， glial activation， inflammation， and abnormalities in oxidative metabolism in specific thalamic regions. TD induces physiological changes including glucose metabolism， oxidative stress， unfolded protein response and accumulation of β-amyloid peptide. A recent study has shown that increasing bioavailability of thiamine can improve the learning and memory ability， decrease accumulation of amyloid protein in the brain of AD mouse. These suggest that thiamine supplementation in the elderly is a promising strategy for preventing Alzheimer’s disease.
Key words: Alzheimer’s disease; accumulation of β-amyloid peptide; neuron loss; metabolic disorder; thiamine
deficiency
