M129M homozygous subjects carrying at least one APOE ε4 allele have a 7.68-fold (p<0.0001) increased risk of developing AD compared to subjects V129V with no APOE ε4 alleles, which is higher than the expected combined effect of the individual contributions of APOE ε4 and PRNP M129M, suggesting gene-gene interaction or epistasis (Table 4, upper). Here, APOE is linked to Alzheimer disease.