Herpes Simplex Virus Infection and in vivo Alzheimer’s Disease Pathologies

Abstract

AbstractBackgroundInterest in the role of Herpes Simplex Virus (HSV) infection in the pathogenesis of Alzheimer’s disease (AD) has increased in recent years. However, previous studies yielded inconsistent findings and no studies have yet investigated the relationship between HSV infection and in vivo AD pathologies such as beta‐amyloid (Aβ) and tau deposition in brain. We examined whether the level of serum anti‐HSV immunoglobulin G (IgG) antibodies (HSV‐IgG), an index of past infection of HSV, is associated with in vivo Aβ and tau deposition in nondemented individuals. We also investigated the modulating effect of HSV‐IgG titer on the relationship between Aβ and tau deposition.MethodA total of 426 nondemented older individuals (55‐90 years old) were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE) cohort. All participants underwent comprehensive clinical assessment, [11C]‐Pittsburgh Compound B positron emission tomography (PET), and blood sampling for measurement of serum HSV antibodies. A subset of participants (N = 129) underwent [18F] AV‐1451 PET. Individuals whose HSV‐IgG titer was lower than 25 percentile of the whole group was classified as the HSVlow group, while those with HSV‐IgG titer higher than 25 percentile were classified as the HSVhigh group.ResultThere was no significant difference in age, sex, clinical diagnosis (cognitive normal vs. mild cognitive impairment), and apolipoprotein E e4 positivity (APOE4) between the HSVlow (N = 106) and HSVhigh (N = 320) groups. In terms of AD biomarkers, neither global Aβ nor tau deposition was different between the HSVhigh and HSVlow groups, even after controlling the effect of age, sex, and APOE4. However, there was a significant HSV group x Aβ deposition interaction effect on tau deposition (p = 0.037), suggesting the level of HSV‐IgG modulates the relationship between Aβ and tau deposition. Subsequent subgroup analyses showed a significant positive association between Aβ and tau deposition only in the HSVhigh group (p < 0.001), but not in the HSVlow group.ConclusionOur finding suggests that past HSV infection may aggravate the influence of Aβ on tau deposition. In regard of AD prevention, the result also supports that more attention needed to be paid to controlling HSV infection.