Shrimpton Antony E, Schelper Robert L, Linke Reinhold P, Hardy John, Crook Richard, Dickson Dennis W, Ishizawa Takashi, Davis Richard L
Department of Pathology, SUNY Upstate Medical University, 750 E Adams St, Syracuse, NY 13210, USA.
Neuropathology. 2007 Jun;27(3):228-32. doi: 10.1111/j.1440-1789.2007.00766.x.
Over 100 mutations in the presenilin-1 gene (PSEN1) have been shown to result in familial early onset Alzheimer disease (EOAD), but only a relatively few give rise to plaques with an appearance like cotton wool (CWP) and/or spastic paraparesis (SP). A family with EOAD, seizures and CWP was investigated by neuropathological study and DNA sequencing of the PSEN1 gene. Abeta was identified in leptomeningeal vessels and in cerebral plaques. A single point mutation, p.L420R (g.1508T > G) that gives rise to a missense mutation in the eighth transmembrane (TM8) domain of PS1 was identified in two affected members of the family. p.L420R (g.1508T > G) is the mutation responsible for EOAD, seizures and CWP without SP in this family.
早老素-1基因（PSEN1）上超过100种突变已被证明会导致家族性早发性阿尔茨海默病（EOAD），但只有相对少数的突变会产生外观类似棉絮状的斑块（CWP）和/或痉挛性截瘫（SP）。通过对PSEN1基因进行神经病理学研究和DNA测序，对一个患有EOAD、癫痫和CWP的家系进行了调查。在软脑膜血管和脑斑块中发现了淀粉样β蛋白（Aβ）。在该家系的两名患病成员中鉴定出一个单点突变，即p.L420R（g.1508T>G），该突变在早老素1（PS1）的第八个跨膜（TM8）结构域中产生错义突变。p.L420R（g.1508T>G）是该家系中导致EOAD、癫痫和CWP但无SP的突变。
