Analysis of the 5th and 8th exon mutation in presenilin-1 gene in sporadic Alzheimer disease

Wu Qi; Fang Ying-ying; Han Jie

doi:10.3321/j.issn:1673-8225.2005.37.021

Abstract：BACKGROUND: Most cases of early-onset familial Alzheimer disease (AD) are associated with presenilin-1 mutation, which mainly occurs in the 5th and 8th exons. Except for the onset age and family history, sporadic AD is basically the same as early-onset familial AD regarding clinical manifestations and pathological characteristics. Is its pathogenesis also related to the mutation of presenilin-1 gene?OBJECTIVE: To probe into the relationship between sporadic AD and presenilin-1 mutation.DESIGN: Case control analysis based on clinical diagnosis.SETTING: Neurology Department of the First Hospital Affiliated to Sun Yat-sen University.PARTICIPANTS: Outpatients who came to the Memory Obstacle Clinic of the First Hospital Affiliated to Sun Yat-sen University between April 1998 and June 2000 but without familial history of AD were selected and divided into 3 groups: [1] AD group: There were 68 cases confirmed as probable having AD according to the clinical diagnostic standard of NINCDS-ADRDA. [2] Vascular dimentia (VaD) group: There were 25 cases confirmed as probable having vascular dimentia according to the clinical diagnostic standard of NINCDS-ADRDA. [3] Normal control group: There were 20 healthy elders (spouses of some patients in the above two groups)without dimentia.METHODS: The conventional phenol extraction method was used to withdraw DNA from peripheral blood, and polymerase chain reaction-single strand conformation polymorphism analysis (PCR-SCCP) was applied to detect the mutation of the 5th and 8th exons in presenilin-1 gene.RESULTS: All the 5th and 8th exons in presenilin-1 gene were proved to be composed of two single strands and a double strand by PCR-SCCP analysis.No abnormal electrophoresis was found, suggesting no that mutation occurred.CONCLUSION: Sporadic AD differs from familial AD in pathogenicity;mutation does not occur or seldom occurs in the 5th and 8th exons in presenilin-1 gene, thereby cannot be considered as an important causive factor for sporadic AD.