Herpes Simplex Virus Implicated in Alzheimer's Disease Development

Herpes simplex virus type 1 (HSV-1), responsible for cold sores around the mouth, may play a crucial role in the development of Alzheimer's disease, according to a significant study funded by pharmaceutical company Gilead Sciences and published in the open-access journal 'BMJ Open'.

The study suggests that antiviral therapy is linked to a reduced risk of this type of dementia, indicating that treatment to alleviate HSV-1 symptoms may offer protective benefits.

Currently, around 35.6 million people globally live with dementia, with 7.7 million new cases diagnosed annually, researchers note. Alzheimer's disease accounts for 60% to 80% of all dementia cases, with total treatment costs reaching $305 billion in 2020.

Various infectious agents have been implicated in Alzheimer's development, with HSV-1 being the most studied. In 2016 alone, it affected over two-thirds of those under 50 worldwide. To shed more light on HSV-1's role in Alzheimer's and the potential protective effects of anti-herpetic drugs, researchers used a large U.S. administrative claims dataset (IQVIA PharMetrics Plus) from 2006 to 2021.

Individuals diagnosed with Alzheimer's were matched by age, sex, geographic region, database entry year, and healthcare visits with those without neurological disease history, resulting in 344,628 case-control pairs. Nearly two-thirds (65%) of those with Alzheimer's were women, with an average age of 73, and tended to have more coexisting conditions, all risk factors. In total, 1,507 individuals (just under 0.5%) with Alzheimer's had been diagnosed with HSV-1 (0.44%), compared to 823 (just under 0.25%) in the control group.

As expected, the risk of Alzheimer's increased with age. However, overall, the likelihood of an HSV-1 diagnosis was 80% higher among those with Alzheimer's, after adjusting for potentially influential factors.

Among the 2,330 individuals with a history of HSV-1 infection, 931 (40%) used anti-herpetic drugs after diagnosis. Additionally, they were 17% less likely to develop Alzheimer's than those who did not use these treatments.

Researchers also examined the potential role of other herpes viruses, such as HSV-2, varicella-zoster virus, and cytomegalovirus. Both HSV-2 and varicella-zoster infections were associated with an increased risk of Alzheimer's. Researchers note that it is unclear exactly how HSV-1 and other neurotropic viruses might increase dementia risk. "However, studies have shown that inflammatory changes in the brain caused by HSV infection are central to the development [of Alzheimer's disease]," they explain.

It has been reported that A epsilon peptides deposit in response to HSV infection and protect host cells by blocking viral fusion with the plasma membrane, indicating that HSV is a potential risk factor for Alzheimer's disease. Consistently, A epsilon exhibits antimicrobial properties against various pathogens, including HSV-1, they add.

HSV-1 DNA is also found in the characteristic plaques of Alzheimer's disease, and individuals carrying the ApoE e4 allele, the most common genetic risk factor for the disease, are more susceptible to HSV infections, they point out.

This is an observational study, and therefore, definitive conclusions about causal relationships cannot be drawn. Researchers acknowledge that HSV-1 infections were unknown before patient inclusion in the database, and many infected individuals are asymptomatic, while others may not seek treatment when symptomatic; all these factors could influence the findings.

But their findings align with those of other studies. They suggest: "While the molecular mechanisms have yet to be fully elucidated, these results indicate a potential role for anti-herpetic therapy in mitigating dementia risk."

"These findings further emphasize considering herpes virus prevention as a public health priority," they conclude.