Association study of late onset Alzheimer's disease with APOC-II gene

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Pericak-Vance (1991) reported that late-onset familial Alzheimer's disease (AD) was linked to the long arm of chromosome 19. Schellenberg (1992) also reported that apolipoproteinC-II (ApoC-II) gene on the chromosome 19q13.2 region was linked with not early-onset but late-onset familial AD.APOC-II contained four exons and three introns and the 3rd intron was composed of minisatellites. It was found that a two-allele polymorphism in the 3rd intron, whose DNA sequence basis was a variation in the number of tandem repeats of a 40 base tau-like core sequence ; a 375 bp fragment corresponded to an allele with 7 repeat units (allele 1) while a 335bp fragment corresponded to an allele with 6 repeat units (allele 2). We investigated an association between APOC-II and sporadic late-onset AD.The subjects were 33 late-onset AD cases diagnosed according to the criteria of NINCDS-ADRDA and 92 normal controls. We extracted DNA from blood samples and amplified the intron 3 of the APOC-II by PCR.PCR products were electrophoresed in 3% agarose gel and stained by ethidium bromide. We detected the two bands : 375bp (allele 1) and 335bp (allele 2). Thses two bands suggest the existence of genotyper ; 1-1,1-2,2-2. The allele frequencies and the frequencies of genotypes of the controls were not significantly different from those expected from the Hardy-Weinberg equilibrium. The frequency of genotype 1-2 was significantly higher in the late-onset AD patients than in the controls. The frequency of allele 1 was higher in the late-onset patients than in the cotrols. A positve association between APOC-II and sporadic late-onset AD was found. This finding is consistent with earlier association studies with APOC-II polymorphism by Schellenberg (1992). The association we report here indicates that the DNA region with susceptibility to late-onset AD lies APOC-II at the chromosome 19q13.2.