Elevated Epstein-Barr Virus Antibody Level is Associated with Cognitive Decline in the Korean Elderly

Chronic viral infection is implicated in cognitive decline and Alzheimer's disease (AD). Our goal was to identify biomarkers for the development of amnestic mild cognitive impairment (aMCI) from cognitively normal state. To accomplish this, we analyzed plasma IgG levels against Epstein-Barr virus (EBV) and herpes simplex virus 1 (HSV-1) in study subjects with incident aMCI (Converter) and normal cognitive function (NC Control) who did or did not convert from cognitively normal state to aMCI during the 2-year follow-up period, respectively. The Converter group exhibited elevated levels of anti-EBV IgG antibodies in the post-follow-up phase (aMCI state) compared to the pre-follow-up phase (cognitively normal state), but not the NC Control group. In contrast, the total IgG level was not significantly changed over the follow-up period. Moreover, elevated anti-EBV IgG levels were significantly associated with CDR scales and total CERAD scores in the Converter group. These results suggest that EBV infection or its related host immune response is linked to cognitive decline. Thus, an EBV antibody level may be used as a potential biomarker for assessing the risk of aMCI development, implying a role for chronic EBV infection in AD pathogenesis.