OBJECTIVE: To explore the effect of mutation of presenilin-1 (PS-1) gene on the pathogenesis of familial Alzheimer disease (FAD). METHODS: Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), denaturing high performance liquid chromatography (DHPLC), and DNA sequencing were used to detect the exons 4 and 5 of PS-1 gene of a 130-member family and a 50-member control group. RESULT: PCR-SSCP showed abnormality in PS-1 exon 5 among 5 AD patients and 4 AD family members without AD symptoms. DHPLC further showed double peaks in the electrophoretic curves of the above nine persons, indicating the possibility of mutation. DNA sequencing revealed a missense mutation of GCT to GGT in code 136 of PS-1 exon 5, leading to the substitution of Ala with Gly (Ala136Gly), in these 9 persons. No mutation in exon 4 was found among these subjects. Mutation in exon 4 and 5 was not found in other members of both this AD family and the control group. CONCLUSION: The mutation in exon 5 of PS-1 gene, found in this AD family, may be one of the responsible PS-1 gene mutations for familial Alzheimer disease in Chinese.