Abstract
Human herpesviruses have previously been implicated in the pathogenesis of Alzheimer’s disease (AD) but whether they are causal, facilitating, or confounding factors is yet to be established. A total of 50 AD subjects and 52 non-demented (ND) controls were analyzed in a multiplex assay for IgG reactivity toward herpes simplex virus (HSV), varicella zoster virus (VZV), cytomegalovirus (CMV), and human herpesvirus 6 (HHV-6). The HHV-6 IgG reactivity was significantly lower in AD subjects compared to ND controls, whereas there were no differences in HSV, VZV, or CMV antibody levels between the groups. Analysis of peripheral blood mononuclear cells with a subtype-specific HHV-6 PCR revealed no signs of reactivation, as AD and ND subjects presented with comparable HHV-6 DNA levels in PBMCs, and all positive samples were of subtype B. Whether HHV-6 is a factor in AD remains to be elucidated in future studies.
Highlights
It has been debated whether infectious agents are causing, triggering, or facilitating the most common age-related diseases, such as cardiovascular disease, dementia, diabetes, and cancer
Human herpesviruses are widely spread in the population, with the seroprevalence of varicella zoster virus (VZV), Epstein–Barr virus (EBV), cytomegalovirus (CMV), and human herpesvirus 6 (HHV-6) increasing rapidly in the first years of life, whereas herpes simplex virus (HSV) infection generally occurs at more advanced ages [3,4,5,6]
We have investigated whether patients with Alzheimer’s disease (AD) present with a different herpesvirus-specific serologic pattern compared to ND controls, using an in-house multiplex IgG immunoassay with antigens generated by lysis of purified virions from infected cells
Summary
It has been debated whether infectious agents are causing, triggering, or facilitating the most common age-related diseases, such as cardiovascular disease, dementia, diabetes, and cancer. Human herpesviruses are widely spread in the population, with the seroprevalence of varicella zoster virus (VZV), Epstein–Barr virus (EBV), cytomegalovirus (CMV), and human herpesvirus 6 (HHV-6) increasing rapidly in the first years of life, whereas herpes simplex virus (HSV) infection generally occurs at more advanced ages [3,4,5,6]. Alzheimer’s disease (AD), with approximately 36.5 million people currently affected worldwide, is the most common form of dementia, causing substantial suffering for patients and a heavy burden on caretakers [12]. Studies of AD postmortem brain tissue have shown an increased prevalence of HSV-1 DNA in patients carrying the ApoE ε4 allele and HHV-6 DNA regardless of ApoE genotype [8]
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