Houlden H, Baker M, McGowan E, Lewis P, Hutton M, Crook R, Wood N W, Kumar-Singh S, Geddes J, Swash M, Scaravilli F, Holton J L, Lashley T, Tomita T, Hashimoto T, Verkkoniemi A, Kalimo H, Somer M, Paetau A, Martin J J, Van Broeckhoven C, Golde T, Hardy J, Haltia M, Revesz T
Department of Clinical Neurology and Neuropathology, Institute of Neurology, London, UK.
Ann Neurol. 2000 Nov;48(5):806-8.
We describe 3 new families affected by Alzheimer's disease with spastic paraparesis. In affected individuals, including the earliest known patient with this clinical syndrome, neuropathological examination revealed large "cotton wool" plaques similar to those we have previously described in a Finnish family. In the families in which DNA was available, presenilin-1 mutations were observed. Transfection of cells with these mutant genes caused exceptionally large increases in secreted Abeta42 levels. Furthermore, brain tissue from individuals with this syndrome had very high amyloid-beta concentrations. These findings define the molecular pathogenesis of an important subgroup of Alzheimer's disease and have implications for the pathogenesis of the disease in general.
我们描述了3个受伴有痉挛性截瘫的阿尔茨海默病影响的新家族。在受影响的个体中，包括已知患有这种临床综合征的最早患者，神经病理学检查发现了与我们之前在一个芬兰家族中描述的相似的大型“棉絮状”斑块。在可获取DNA的家族中，观察到了早老素-1突变。用这些突变基因转染细胞导致分泌的β淀粉样蛋白42水平异常大幅升高。此外，患有这种综合征的个体的脑组织中β淀粉样蛋白浓度非常高。这些发现确定了阿尔茨海默病一个重要亚组的分子发病机制，并对该疾病的总体发病机制具有启示意义。
