Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
J Alzheimers Dis. 2010;20(1):43-7. doi: 10.3233/JAD-2010-1369.
Alzheimer's disease (AD) is characterized by accumulation of toxic amyloid-beta (Abeta) in the brain, with neuronal death, and an associated increased Abeta(42/40) ratio. Several mutations in presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid-beta precursor protein are involved in the etiology of familial AD (FAD); these mutations alter the Abeta(42/40) ratio and promote apoptosis. We describe an Italian pedigree linked to a novel mutation (S175C) at the third transmembrane domain of PSEN2. Clinical phenotype in these individuals is characterized by fast cognitive decline with progressive memory impairment, early involvement of executive functions, behavioral disturbances, and extrapyramidal signs.
阿尔茨海默病（AD）的特征是大脑中有毒的淀粉样β（Abeta）积累，导致神经元死亡，以及相关的 Abeta（42/40）比值升高。早老素 1（PSEN1）、早老素 2（PSEN2）和淀粉样前体蛋白中的几种突变参与家族性 AD（FAD）的发病机制；这些突变改变了 Abeta（42/40）比值并促进细胞凋亡。我们描述了一个与 PSEN2 第三跨膜结构域的新型突变（S175C）相关的意大利家系。这些个体的临床表型特征是认知能力迅速下降，伴有进行性记忆障碍、执行功能早期受累、行为障碍和锥体外系体征。
