Abstract
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(1-40) [Aβ40], Aβ(1-42) [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.