Herpes: Risk Factor for Alzheimer Disease?

With 90% of the population containing latent HSV1, researchers found the factors that connect with Alzheimers diagnoses.


Herpes simplex virus (HSV) has been linked to dementia and Alzheimer disease (AD) for several decades. Herpes simplex virus 1 (HSV1) has been found in brain tissue from patients with AD and located specifically within amyloid plaques. But as much as 90% of the population has latent HSV1 infection—so why doesn’t everyone get AD? Two recent studies help clarify some of the possible reasons.

Researchers from Umeå University, Sweden, analyzed prospective plasma samples from 360 well-defined AD cases and 360 dementia-free controls. All AD cases were initially examined at the University Hospital Memory Clinic and later reviewed by an experienced specialist in psychogeriatric medicine. The plasma samples were, in most cases, taken a mean of 9.6 years before the AD diagnosis.

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The presence of anti-HSV immunoglobulin G (IgG) antibodies doubled the risk of AD among patients whose plasma samples were taken > 6 years before the AD diagnosis. That confirms previous findings that indicated a role of HSV infection in the early development of AD, the researchers say. The HSV-associated risk for AD seemed to be higher among patients aged > 60 years at the time of the sampling and among women (although women had a higher mean age in this study).

The researchers advise that their findings should be interpreted with caution. For one, because so many people carry HSV, additional factors must be considered as modifiers of the HSV-associated risk of AD, such as an individual’s humoral immune response to infection. They also point to hypotheses that a weakened immune system in an older person might contribute to HSV reactivation, which could spread to the brain, whereas other non-HSV causes might be more common among younger people.

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A second study at the same university found a higher risk of AD with reactivated herpes infection. The researchers followed 3,432 adults enrolled in an ongoing longitudinal study. Serum samples were analyzed for anti-HSV antibodies (IgG and IgM); 3,026 (88%) had anti-HSV antibodies at baseline.

During the follow-up period, a mean of 11.3 years, 430 people developed a dementia disorder, including 245 who developed AD. The presence of anti-HSV IgG antibodies did not increase the risk of AD, but anti-HSV IgM antibodies, a sign of reactivated infection, nearly doubled it. The risk for AD did not seem to increase until about 8 to 10 years after a positive anti-HSV IgM serum sample, the researchers say, possibly pointing toward HSV reactivation being an early event in the development of AD pathology.

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Although the strengths of the study included the large sample, long follow-up, and “extensive and repeated” diagnostic evaluations, the researchers note that only a small number of people were positive for anti-HSV IgM antibodies, and the APOE genotype was not available for all participants. However, they also point out that anti-HSV IgM antibodies are relatively short-lived and uncommon in the general population. They suggest that a possible explanation for their major finding—the higher risk with HSV reactivation—is that a combination of HSV1 and certain host immunologic factors that permit reactivation from latency and possibly spread to the central nervous system “constitutes the real risk for AD.”

Sources: Lövheim H, Gilthorpe J, Johansson A, Eriksson S, Hallmans G, Elgh F. Alzheimers Dement. 2015:11(6):587-592.
doi: 10.1016/j.jalz.2014.07.157.
Lövheim H, Gilthorpe J, Adolfsson R, Nilsson L-G, Elgh F. Alzheimers Dement. 2015;11(6):593-599.
doi: 10.1016/j.jalz.2014.04.522.

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