Matsuyama S S, Jarvik L F
West Los Angeles VA Medical Center, CA 90073.
Proc Natl Acad Sci U S A. 1989 Oct;86(20):8152-6. doi: 10.1073/pnas.86.20.8152.
Alzheimer disease (AD) is a clinicopathologic syndrome of unknown etiology with numerous abnormalities in neuronal and nonneuronal cells. A review of the literature suggests that a common basic intracellular defect may underlie many of the reported abnormalities. We hypothesize impairment of the microtubule (MT) system as one explanation for the pathogenesis of AD. Evidence in support of the hypothesis includes the following: MTs are ubiquitous and vital cell components, unequally distributed, with the highest concentration in the brain; various abnormalities, including the key neuropathologic lesions, can be explained by impairments of the MT system; and experiments utilizing pharmacologic agents known to disrupt MTs have reproduced certain abnormalities observed in AD. The hypothesis provides a framework for systematic investigations of MTs at the cellular and molecular levels as well as the basis for in vivo diagnostic tests for AD.
阿尔茨海默病（AD）是一种病因不明的临床病理综合征，在神经元和非神经元细胞中存在众多异常。文献综述表明，一种常见的基本细胞内缺陷可能是许多已报道异常的基础。我们假设微管（MT）系统受损是AD发病机制的一种解释。支持该假设的证据如下：微管是普遍存在且至关重要的细胞成分，分布不均，在大脑中浓度最高；包括关键神经病理病变在内的各种异常可以用微管系统受损来解释；利用已知会破坏微管的药物进行的实验重现了AD中观察到的某些异常。该假设为在细胞和分子水平上对微管进行系统研究提供了框架，也是AD体内诊断测试的基础。
