Herpes and Alzheimer’s: A New Scientific Connection

Alzheimer’s disease (AD), a neurodegenerative condition that robs individuals of memory and cognitive function, has long been associated with aging and genetic risk factors. However, recent research is shifting that narrative. A groundbreaking study published in BMJ Open in May 2025 has reignited the conversation around the herpes simplex virus type 1 (HSV-1)—commonly responsible for cold sores—and its potential role in triggering Alzheimer’s. This article explores these new findings in depth, including how antiviral treatments may reduce the risk of developing AD.

Understanding Herpes Simplex Virus Type 1

HSV-1 is a widespread virus known to cause oral herpes, typically manifesting as cold sores. It infects the majority of the global population and can lie dormant in the nervous system for years. Periodic reactivations of HSV-1 are common and are usually considered benign. However, the virus’s ability to reside in the nervous system is what makes it a potential suspect in neurological conditions like Alzheimer’s.

Alzheimer’s Disease: A Brief Overview

Alzheimer’s disease is marked by the accumulation of amyloid-beta plaques and neurofibrillary tangles of tau protein in the brain. These lead to the loss of neurons and synapses, ultimately resulting in cognitive decline and dementia. Traditional risk factors include aging, genetic variants like APOE ε4, and lifestyle elements such as cardiovascular health and education level. But now, infectious agents are gaining attention as potential contributors.

Key Findings from the 2025 BMJ Open Study

Published on May 20, 2025, in BMJ Open, a large-scale cohort study analyzed data from over 344,000 individuals aged 50 and above in the United States to examine whether HSV-1 infection influences the risk of Alzheimer’s disease.

• 80% Increased Risk: Individuals diagnosed with HSV-1 had an 80% higher risk of developing Alzheimer’s compared to those without the infection.
• 17% Risk Reduction from Antivirals: Among those with HSV-1, patients who received antiviral treatment (e.g., acyclovir or valacyclovir) had a 17% lower risk of developing Alzheimer’s than untreated individuals.
• Prevalence: HSV-1 was documented in 0.44% of Alzheimer’s cases, suggesting it is not a predominant cause but may be a significant risk factor for a subset of patients.

These findings underscore the relevance of herpes management in discussions about dementia prevention.

Mechanistic Insights and Prior Research

While the 2025 BMJ Open study adds robust statistical evidence, it builds on decades of mechanistic research suggesting that HSV-1 can contribute to Alzheimer’s pathology:

• Dr. Ruth Itzhaki’s work from the University of Manchester highlighted that HSV-1 resides in the brain and reactivates, especially in APOE ε4 carriers, promoting amyloid and tau accumulation.
• Wozniak et al. (2009) found HSV-1 DNA within amyloid plaques in Alzheimer’s brains.
• In vitro studies (e.g., De Chiara et al., 2010) show HSV-1 infection increases amyloid-beta and tau abnormalities in neuronal cultures.

How HSV-1 May Contribute to Alzheimer’s

The biological mechanisms proposed to explain HSV-1’s potential contribution to Alzheimer’s include:

1. Chronic Neuroinflammation: Reactivation of HSV-1 triggers inflammatory responses, damaging neurons over time.
2. Amyloid Defense Hypothesis: Amyloid-beta may serve as an antimicrobial peptide, accumulating in response to HSV-1.
3. Oxidative Stress and DNA Damage: HSV-1 induces cellular stress and damages DNA, potentially compromising neuron integrity.

The Promise of Antiviral Treatment

One of the most actionable findings from the 2025 BMJ Open study is the observed reduction in Alzheimer’s risk with antiviral use. This aligns with earlier work from Tzeng et al. (2018), who found a similar trend in Taiwanese cohorts.

Antiviral drugs such as acyclovir and valacyclovir suppress HSV-1 reactivation, potentially mitigating inflammatory and amyloidogenic processes in the brain. This opens a potential new avenue for Alzheimer’s prevention, particularly for HSV-1 carriers and APOE ε4 positive individuals.

Challenges and Controversies

While the association is compelling, some scientists caution against inferring causation from correlation. Dr. John Hardy from University College London notes that while the viral hypothesis is plausible, more direct causal evidence is needed. Additionally, the relatively low HSV-1 prevalence among Alzheimer’s patients (0.44%) implies that other mechanisms are also at play.

Future Research Directions

Current and future studies aim to better understand the causality and therapeutic implications of this link. Notably, Dr. Hugo Lövheim of Umeå University is leading a randomized clinical trial to evaluate the impact of antiviral treatment on cognitive outcomes in Alzheimer’s patients.

Other studies are exploring biomarkers that can detect latent HSV-1 activity in the brain, which could be critical for identifying at-risk individuals early in the disease process.

The 2025 BMJ Open study provides some of the strongest evidence to date linking HSV-1 infection with Alzheimer’s disease, and suggests that antiviral treatment may play a preventative role. These findings, when combined with prior mechanistic research, highlight the potential for a new paradigm in Alzheimer’s prevention that includes managing chronic viral infections.

As the field advances, public health initiatives may increasingly prioritize herpes management and antiviral access—not only for symptomatic relief but potentially for neurodegenerative disease prevention as well.