Guyant-Maréchal L, Campion D, Hannequin D
Service de neurologie, CHU de Rouen, 1, rue de Germont, 76031 Rouen cedex, France.
Rev Neurol (Paris). 2009 Mar;165(3):223-31. doi: 10.1016/j.neurol.2008.10.019. Epub 2008 Dec 10.
We propose a review devoted to the autosomal dominant forms of Alzheimer disease (AD). These forms are the consequences of either PSEN1 mutations (69%), APP mutations (1%), or APP duplication (7.5%), and exceptionally of PSEN2 mutations (2%). The main characteristic of these AD forms is the early age of onset usually before the age of 60 years. The first part of the review focuses on the identification of unusual clinical and neuropathological phenotypes enlarging the AD spectrum: intracerebral hemorrhages caused by severe amyloid angiopathy, spastic paraparesis, Lewy body dementia and exceptional cerebellar ataxia. The second part concerns the consequences of these mutations on A beta processing, thus demonstrating the key role of the causal "amyloid cascade".
我们提议进行一项关于常染色体显性阿尔茨海默病(AD)形式的综述。这些形式是由PSEN1突变(69%)、APP突变(1%)或APP重复(7.5%)导致的,极少数情况下是由PSEN2突变(2%)引起的。这些AD形式的主要特征是发病年龄较早,通常在60岁之前。综述的第一部分着重于识别扩大AD谱的不寻常临床和神经病理学表型:严重淀粉样血管病引起的脑出血、痉挛性截瘫、路易体痴呆和罕见的小脑共济失调。第二部分涉及这些突变对β-淀粉样蛋白加工的影响,从而证明了因果性“淀粉样蛋白级联反应”的关键作用。