Objectives: To explore the role of the polymorphism of 3'-terminal intron of the eight exon of presenilin-1 gene in the pathogenesis of sporadic Alzheimer disease (SAD). Methods: The polymorphism of 3'-terminal intron of the eight exon of presenilin-1 (PS-1) gene was detected by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique in 75 patients with SAD and 73 normal controls. Results: Comparing to controls, the frequencies of 1 alleles of PS-1 gene in patients with SAD increased obviously (P < 0.01, RR = 1.83), while the frequencies of 2 alleles were decreased obviously (P < 0.01, RR = 0.55), and the 2/2 genotypes of PS-1 gene in patients with SAD decreased (P < 0.05, RR = 0.32). Conclusion: Our result indicated that the polymorphism of PS-1 gene was associated obviously with SAD the onset of SAD was negatively associated with 2 alleles of PS-1 gene, and was positively associated with 1 alleles of PS-1 gene. 2 alleles of PS-1 gene may protect people from SAD, 1 alleles of PS-1 gene may increase the risk of the onset of SAD.