Human herpes viruses are associated with steeper age-dependent increases of serum biomarkers for dementia in cognitively unimpaired women.

Blood biomarkers for dementia are being increasingly used for screening and possibly early detection of dementia in cognitively unimpaired (CU) people. Here we measured blood serum levels of 5 dementia-related biomarkers (Aβ [Aβ40], Aβ [Aβ42], Aβ42/Aβ40 ratio, phosphorylated Tau181 [pTau181], and phosphorylated Tau217 [pTau217]) and determined the seroprevalence of 6 HHV (HHV1, HHV2, HHV3, HHV4, HHV5, HHV6) in 345 samples drawn at successive visits from 167 CU women 26-98 years old. All biomarkers except for Aβ42/Aβ40 increased significantly with age, particularly in those who were HHV seropositive. With respect to the biomarkers, the increase was highest for Aβ40 > Aβ42 > pTau217 > pTau181, and, with respect to HHV, the increase was highest for HHV4 > HHV6 > HHV1 > HHV2 > HHV5 (HHV3 was seropositive in all samples). Overall, the average normalized rate of increase of biomarkers with age was 2.15 × higher in the HHV seropositive vs. seronegative groups (P = 0.003, paired samples t-test). The presence of apolipoprotein E4 (apoE4) genotype did not have a significant effect on those rates. These findings document a link between prior viral infection and dementia-related blood biomarkers, adding support to the HHV hypothesis in developing dementia, irrespective of apoE4 allele presence.