Interaction between Cytomegalovirus and Herpes Simplex Virus Type 1 Associated with the Risk of Alzheimer’s Disease Development

Article type: Research Article

Authors: Lövheim, Hugo^{a; b; *} | Olsson, Jan^c | Weidung, Bodil^{a; b} | Johansson, Anders^{d; e} | Eriksson, Sture^{a; e} | Hallmans, Göran^e | Elgh, Fredrik^c

Affiliations: [a] Department of Community Medicine and Rehabilitation, Geriatric Medicine, Umeå University, Umeå, Sweden | [b] Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala University, Uppsala, Sweden | [c] Department of Clinical Microbiology, Virology, Umeå University, Umeå, Sweden | [d] Department of Odontology, Umeå University, Umeå, Sweden | [e] Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden

Correspondence: [*] Correspondence to: Hugo Lövheim, Department of Community Medicine and Rehabilitation, Geriatric Medicine, Umeå University, SE-901 85 Umeå, Sweden. Tel.: +46 90 785 88 59; E-mail: hugo.lovheim@umu.se.

Abstract: Background:Several environmental factors, including infectious agents, have been suggested to cause Alzheimer’s disease (AD). Cytomegalovirus (CMV) has been associated with AD in several recent studies. Objective:To investigate whether carriage of CMV, alone or in combination with Herpes simplex virus (HSV), increased the risk of developing AD. Methods:Plasma samples from 360 AD cases (75.3% women, mean age 61.2 years), taken an average of 9.6 years before AD diagnosis, and 360 age-, sex-, cohort-, and sampling date matched dementia-free controls were analyzed to detect anti-CMV (immunoglobulin [Ig] G and IgM), group-specific anti-HSV (IgG and IgM), and specific anti-HSV1 and HSV2 IgG antibodies by enzyme-linked immunosorbent assays. AD cases and dementia-free controls were compared using conditional logistic regression analyses. Results:The presence of anti-CMV IgG antibodies did not increase the risk of AD (odds ratio [OR], 0.857; p = 0.497). Among AD cases, an association between CMV and HSV1 carriage was detected (OR 7.145, p < 0.001); in a conditional logistic regression model, the interaction between CMV and HSV1 was associated with AD development (OR 5.662; p = 0.007). Conclusion:The present findings do not support a direct relationship between CMV infection and the development of AD; however, an interaction between CMV and HSV1 was found to be associated significantly with AD development. These findings suggest that CMV infection facilitates the development of HSV1-associated AD, possibly via its effects on the immune system.

Keywords: Alzheimer’s disease, cytomegalovirus, dementia, Herpes simplex virus, nested case-control study

DOI: 10.3233/JAD-161305

Journal: Journal of Alzheimer's Disease, vol. 61, no. 3, pp. 939-945, 2018