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Researchers Explore Possible Link Between CMV and Alzheimer’s Disease

By August 9, 2016Cytomegalovirus ("CMV")

Alzheimer’s disease (“AD”) is the most common cause of dementia in developed countries and is one of the leading sources of morbidity and mortality in aging populations. Clinical manifestations of AD include memory impairment, decline in executive function, and impaired motor function. Treatments are available that can ameliorate some symptoms of the illness, but there is currently no cure.

AD is thought to be the result of toxic proteins building up in the brain, especially amyloid-β peptides, but the exact cause of the disease is unknown and is believed to be multifactorial. An increasing number of studies suggest that various pathogenic infections, including cytomegalovirus (“CMV”), may be involved in the etiology of AD.

CMV is a common virus that infects one in every two people in many developed countries. Most CMV infections are “silent,” meaning most people who are infected with CMV exhibit no signs or symptoms, however, the infection can be serious in certain patient populations, including newborns, when a mother is infected during pregnancy, and the immunocompromised. In addition, CMV is implicated in a number of chronic conditions where it is thought to act as a proinflammatory agent.

Viral infections can lead to inflammatory conditions that cause the release of cytokines called interferon-γ and tumor necrosis factor-α. These cytokines have been shown to induce the deposition of amyloid-β peptides, one of the hallmarks of AD pathology, an observation that may support the hypothesis that inflammation plays a role in the progression of AD.

Consistent with this hypothesis, CMV is known to infect the central nervous system (“CNS”), provoking a proinflammatory response, which could make it a contributing factor in the development of AD. Some prior research has found an association between patients’ immune responses to CMV and signs of AD.

In a recent study published in The Journal of Infectious Diseases, researchers tested the association between CMV serostatus and AD in a longitudinal study of older individuals examined annually for up to 17 years. Researchers found that CMV seropositivity was associated with a two-fold increase in the risk of AD, and a faster rate of cognitive decline.

To test the specificity of the effect, the researchers repeated the analysis replacing CMV status with herpes simplex virus (“HSV-1”) status. HSV-1 is another member of the herpes virus family that can also lead to inflammatory conditions in the CNS. Researchers have explored the relationship between HSV-1 and AD in the past, but in this study it was found that there was no relationship between HSV-1 status and the risk of AD.

This was the first study of its kind to demonstrate a link between serological evidence of CMV exposure and the risk of AD in the population sampled. The potential mechanism linking CMV with the risk of AD is still being investigated, but the lack of association between HSV-1 status and the risk of AD suggests that the effect of CMV on the risk of AD may be relatively specific and not necessarily generalizable to all chronic infections of the nervous system.

More work is needed to understand the relationship between CMV and the risk of Alzheimer’s disease, especially to understand if there is a direct causal relationship. If a direct relationship can be established, CMV vaccination may be a viable strategy to reduce the incidence of Alzheimer’s disease.