Tabira Takeshi
National Institute for Longevity Sciences, 36-3, Gengo, Morioka, Obu, 474-8522 Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 2002 Oct;22(5):175-80.
It is now widely accepted that beta-amyloid has a central role in the pathogenesis of Alzheimer's disease (AD). It is mainly composed of aggregated A beta protein and is deposited in senile plaques and cerebral blood vessels. However, it is not uncommon to see autopsies that reveal significant deposits of beta-amyloid in the brain without manifesting dementia. In fact, several neuropathological studies showed no correlation between beta-amyloid burden and the severity of dementia or loss of synapses. Thus it is questioned whether extracellularly deposited beta-amyloid is directly linked to the Alzheimer pathomechanism. Here I show evidence to support the significance of intraneuronally deposited A beta x-42 by analyzing presenilin 1 transgenic mice and AD patients.
目前，β-淀粉样蛋白在阿尔茨海默病（AD）发病机制中起核心作用已被广泛接受。它主要由聚集的Aβ蛋白组成，沉积在老年斑和脑血管中。然而，在尸检中发现大脑中有大量β-淀粉样蛋白沉积但未表现出痴呆的情况并不少见。事实上，多项神经病理学研究表明，β-淀粉样蛋白负荷与痴呆严重程度或突触丧失之间没有相关性。因此，细胞外沉积的β-淀粉样蛋白是否与阿尔茨海默病发病机制直接相关受到质疑。在此，我通过分析早老素1转基因小鼠和AD患者来证明神经元内沉积的Aβx-42的重要性。
