Tamaoka Akira
Department of Neurology, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan.
Rinsho Byori. 2013 Nov;61(11):1060-9.
The neuropathological characteristics of the Alzheimer's disease (AD) brain include senile plaques, neurofibrillary tangles and neuronal cell loss extensively recognized in brain cortices. Biochemical studies revealed that senile plaques and neuronfibrillary tangles are composed mainly of amyloid beta protein and highly phosphorylated tau protein, a microtubule-associated protein, respectively. Abeta deposition in senile plaques was previously considered to initiate the pathological cascade of Alzheimer's disease (AD), suggesting that the aggregation of Abeta in insoluble Abeta fibrils plays an important role in its neurotoxicity ('amyloid cascade hypothesis'). However, the concentrations of Abeta required for fibrillization are higher than its physiological concentrations. In addition, cognitive decline in AD patients is not correlated with the levels of senile plaque formation. Currently, AD is believed to begin with synaptic dysfunction caused by soluble Abeta oligomers, playing a more important role in the etiology of AD than insoluble Abeta ibrils ('oligomer hypothesis').
阿尔茨海默病（AD）大脑的神经病理学特征包括老年斑、神经原纤维缠结以及大脑皮层中广泛存在的神经元细胞丢失。生化研究表明，老年斑和神经原纤维缠结分别主要由淀粉样β蛋白和高度磷酸化的tau蛋白（一种微管相关蛋白）组成。老年斑中的淀粉样β蛋白沉积以前被认为启动了阿尔茨海默病（AD）的病理级联反应，这表明不溶性淀粉样β纤维中淀粉样β蛋白的聚集在其神经毒性中起重要作用（“淀粉样蛋白级联假说”）。然而，形成纤维所需的淀粉样β蛋白浓度高于其生理浓度。此外，AD患者的认知能力下降与老年斑形成水平无关。目前，人们认为AD始于可溶性淀粉样β寡聚体引起的突触功能障碍，在AD的病因中，可溶性淀粉样β寡聚体比不溶性淀粉样β纤维起更重要的作用（“寡聚体假说”）。
