INTRODUCTION
The underlying cause of Alzheimer's disease (AD), a progressive neurologic disorder that is the most common cause of dementia, is poorly understood. At present, the treatments currently available have limited or questionable benefits and no known preventative treatments exist.1 6.5 million Americans over 65 have AD and that number is expected to double by 2050. In 2021, 239 billion dollars a year was spent by Medicare on dementia and AD, a figure that represents 67% of total Medicare spending.2 The National Institutes of Health (NIH) spends approximately 3 billion dollars every year on AD research.3 The new drug Aduhelm, conditionally approved by the US Food and Drug Agency (FDA) in June 2021, has been met with controversy due to equivocal data regarding its efficacy, significant side effects, and high cost of treatment.4 Therefore, it may be of benefit to search for therapeutics to treat or prevent AD.
Herpesviridae is a class of viruses that are common causes of mucocutaneous pathologies.5 The lesions caused by them are often benign and self-resolving and, therefore, immediate treatment is often not requested. Specifically, Herpes simplex virus 1 (HSV-1) can lead to commonly seen lesions around the oral mucosa and is often left untreated; however, anti-virals such as acyclovir and valacyclovir are frequently administered to manage more severe, acute infections or frequent outbreaks.5-7
The neurotropic nature of HSV-1, as well as its ability to establish dormancy in the sensory root ganglia of the trigeminal nerve, has made it a target of research as a potential infectious etiology for AD.6 Various pathophysiologic mechanisms centering around neuroinflammation evoked by the virus in genetically susceptible individuals have been proposed.8 Recent studies demonstrate a strong correlation between HSV-1 and AD; however, treatment of HSV-1 for prevention of AD is not currently the standard of care. Due to the high prevalence of HSV-1 in the adult population, focusing on HSV-1 anti-viral suppression may be a reasonable course of action considering the possible link to AD in this cohort.9,10
This review includes a literature search investigating epidemiological associations between AD and infection with Herpesviridae, most notably HSV-1, and reports findings and limitations of the reviewed articles. The included studies take the form of population-based studies of humans. Also, we discuss commonly described pathophysiological mechanisms proposed for this association as well as the clinical relevance for dermatologists. Dermatologists have an important role in AD prevention. Lastly, we believe that, based on the quality of existing evidence, it may be reasonable to treat HSV-1 infections using anti-virals to prevent future development of AD.
Herpesviridae is a class of viruses that are common causes of mucocutaneous pathologies.5 The lesions caused by them are often benign and self-resolving and, therefore, immediate treatment is often not requested. Specifically, Herpes simplex virus 1 (HSV-1) can lead to commonly seen lesions around the oral mucosa and is often left untreated; however, anti-virals such as acyclovir and valacyclovir are frequently administered to manage more severe, acute infections or frequent outbreaks.5-7
The neurotropic nature of HSV-1, as well as its ability to establish dormancy in the sensory root ganglia of the trigeminal nerve, has made it a target of research as a potential infectious etiology for AD.6 Various pathophysiologic mechanisms centering around neuroinflammation evoked by the virus in genetically susceptible individuals have been proposed.8 Recent studies demonstrate a strong correlation between HSV-1 and AD; however, treatment of HSV-1 for prevention of AD is not currently the standard of care. Due to the high prevalence of HSV-1 in the adult population, focusing on HSV-1 anti-viral suppression may be a reasonable course of action considering the possible link to AD in this cohort.9,10
This review includes a literature search investigating epidemiological associations between AD and infection with Herpesviridae, most notably HSV-1, and reports findings and limitations of the reviewed articles. The included studies take the form of population-based studies of humans. Also, we discuss commonly described pathophysiological mechanisms proposed for this association as well as the clinical relevance for dermatologists. Dermatologists have an important role in AD prevention. Lastly, we believe that, based on the quality of existing evidence, it may be reasonable to treat HSV-1 infections using anti-virals to prevent future development of AD.
