Small D H
Department of Pathology, University of Melbourne, Parkville, Victoria, Australia.
Neurochem Res. 1998 May;23(5):795-806. doi: 10.1023/a:1022471729291.
Alzheimer's disease (AD) is the most common form of dementia in the aged population. Early-onset familial AD (FAD) involves mutations in a gene on chromosome 21 encoding the amyloid protein precursor or on chromosomes 14 or 1 encoding genes known as presenilins. All mutations examined have been found to increase the production of amyloidogenic forms of the amyloid protein (A beta), a 4 kDa peptide derived from APP. Despite the remarkable progress in elucidating the biochemical mechanisms responsible for AD, little is known about the normal function of APP. A model of how APP and A beta are involved in pathogenesis is presented. This model may explain why certain neuronal populations are selectively vulnerable in AD. It is suggested that those neurons which more readily undergo neuritic sprouting and synaptic remodelling are more vulnerable to A beta neurotoxicity.
阿尔茨海默病（AD）是老年人群中最常见的痴呆形式。早发性家族性AD（FAD）涉及21号染色体上编码淀粉样蛋白前体的基因或14号或1号染色体上编码早老素的基因突变。所有检测到的突变均已发现会增加淀粉样蛋白（Aβ）的淀粉样生成形式的产生，Aβ是一种源自APP的4 kDa肽。尽管在阐明AD的生化机制方面取得了显著进展，但对APP的正常功能却知之甚少。本文提出了一个关于APP和Aβ如何参与发病机制的模型。该模型可能解释了为什么某些神经元群体在AD中具有选择性易损性。有人认为，那些更容易发生神经突萌发和突触重塑的神经元更容易受到Aβ神经毒性的影响。
