Itzhaki R F
Department of Optometry and Vision Sciences, University of Manchester Institute of Science and Technology, UK.
Mol Neurobiol. 1994 Aug-Dec;9(1-3):1-13. doi: 10.1007/BF02816099.
Inherited cases of Alzheimer's disease (AD) comprise only a very small proportion of the total. The remainder are of unknown etiopathogenesis, but they are very probably multifactorial in origin. This article describes studies on four possible factors: aluminum; viruses--in particular, herpes simplex type I virus (HSV1); defective DNA repair; and head trauma. Specific problems associated with aluminum, such as inadvertent contamination and its insolubility, have led to some controversy over its usage. Nonetheless, the effects of aluminum on animals and neuronal cells in culture have been studied intensively. Changes in protein structure and location in the cell are described, including the finding in this laboratory of a change in tau resembling that in AD neurofibrillary tangles, and also the lack of appreciable binding of aluminum to DNA. As for HSV1, there has previously been uncertainty about whether HSV1 DNA is present in human brain. Work in this laboratory using polymerase chain reaction has shown that HSV1 DNA is present in many normal aged brains and AD brains, but is absent in brains from younger people. Studies on DNA damage and repair in AD and normal cells are described, and finally, the possible involvement of head trauma is discussed.
遗传性阿尔茨海默病（AD）仅占总数的极小比例。其余病例的病因发病机制不明，但很可能是多因素起源。本文描述了对四个可能因素的研究：铝；病毒——特别是单纯疱疹病毒I型（HSV1）；有缺陷的DNA修复；以及头部创伤。与铝相关的特定问题，如意外污染及其不溶性，导致了对其用途的一些争议。尽管如此，人们对铝对动物和培养中的神经元细胞的影响进行了深入研究。文中描述了细胞中蛋白质结构和位置的变化，包括本实验室发现的tau蛋白变化类似于AD神经原纤维缠结中的变化，以及铝与DNA缺乏明显结合。至于HSV1，以前人们不确定HSV1 DNA是否存在于人类大脑中。本实验室利用聚合酶链反应开展的研究表明，HSV1 DNA存在于许多正常老年大脑和AD大脑中，但在年轻人的大脑中不存在。文中描述了对AD细胞和正常细胞中DNA损伤与修复的研究，最后讨论了头部创伤可能的影响。
