Epistatic effects of immunoglobulin KM (κ marker) allotypes and <i>APOE</i> ε4 allele on the risk of Alzheimer's disease

We investigated whether immunoglobulin KM (κ marker) allotypes were associated with Alzheimer's disease (AD) individually and/or epistatically with <i>APOE</i> ε4, the strongest known genetic susceptibility factor for the disease. Results showed a significant (p = 0.01) interaction between KM and <i>APOE</i> ε4. In KM 3/3 homozygotes, <i>APOE</i> ε4 was strongly associated with AD (OR = 8.3); however, in non-KM 3/3 subjects, the association between <i>APOE</i> ε4 and AD was markedly lower (OR = 0.9) and non-significant. If confirmed, these results may identify a subgroup of the population with a markedly higher risk of developing AD, who might require a different preventive/treatment strategy.