Cleveland Clinic Researchers Uncover Herpes-Alzheimer’s Link and Potential Treatment
A team from Cleveland Clinic’s Genome Center has mapped the pathway through which herpes simplex virus-1 (HSV-1) may contribute to Alzheimer’s disease in aging brains. Their findings, published in Alzheimer's & Dementia: The Journal of the Alzheimer's Association, provide the first direct evidence supporting the controversial connection between herpesviruses and neurodegeneration. The study also identifies two FDA-approved antiviral drugs that reverse this pathway in laboratory settings.

The Impact of Herpes Infections
For most individuals, herpes infections are mild or asymptomatic, with many carrying multiple herpesviruses throughout life. While generally harmless when suppressed, research suggests that as the immune system weakens with age, herpesviruses can reactivate, potentially contributing to various health conditions—including neurodegenerative diseases like Alzheimer's.

The Role of Transposable Elements in Alzheimer’s
Dr. Feixiong Cheng, senior author and director of the Genome Center, hypothesized that latent HSV-1 infections might contribute to Alzheimer’s by activating transposable elements (TEs)—small DNA sequences that move within the genome, disrupting gene function. TEs become more active with age and have been previously linked to neurodegeneration.

By analyzing large-scale RNA sequencing data from both healthy and Alzheimer’s-affected brains, the researchers found that HSV-1 infection was associated with increased TE activation, leading to:

HSV-1 reactivation with age
Activation of TEs like LINE-1, known to disrupt brain function
Accumulation of Alzheimer’s-associated proteins like Tau
Neuroinflammation and neurodegeneration
Potential Treatment with Antiviral Drugs
The team then used artificial intelligence to analyze 80 million patient health records, revealing that individuals prescribed antiviral herpes medications—valacyclovir and acyclovir—had a significantly lower incidence of Alzheimer’s. Laboratory models confirmed that these drugs could reverse the HSV-1–Alzheimer’s pathway, providing promising therapeutic insights.

Dr. Cheng emphasized that these findings not only strengthen the herpes-Alzheimer’s connection but also offer potential treatment strategies for other neurological diseases linked to herpesviruses. The study involved collaborations with researchers from Case Western Reserve University, Johns Hopkins University, the University of Nevada Las Vegas, and Cleveland Clinic’s Lou Ruvo Center for Brain Health.

Source: https://www.lerner.ccf.org/news/article/?title=Herpesviruses+may+contribute+to+Alzheimer%E2%80%99s+disease+via+transposable+elements&id=6f3b066966f51175583b264360ae95904428404b