https://www.statnews.com/2025/01/07/alzheimers-disease-research-link-between-herpes-virus-head-trauma-dementia/ Skip to Main Content STAT * Manage alerts for this article * Email this article * Share this article Donald Trump scientists Vaccines * Newsletters * Log In * My Account * Subscribe Now My Account * Settings Complete your personal information for a more tailored experience * Billing * Log Out STAT Reporting from the frontiers of health and medicine * Newsletters * Log In * My Account * Subscribe Now * Biotech * Pharma * Public Health * Health Tech * Policy * Science * First Opinion * STAT+ * STAT Events * STAT [ ] Search * Log In * Try STAT+ * My Account Home News * Latest * Business + Biotech + Pharma + Health Tech + Health Insurance + Hospitals + Medical Devices * Washington + Policy + FDA + CDC + NIH * Science + CRISPR + Gene Therapy + Research + Neuroscience * Public Health + H5N1 Bird Flu + Addiction + Covid-19 + Abortion + Health Disparities + Infectious Disease + Mental Health * Disease + Cancer + Cardiovascular Disease + Chronic Disease + Diabetes + Alzheimer's + Obesity * Features + Coercive Care + The Obesity Revolution + The War on Recovery Newsletters Opinion Columns * Adam Feuerstein * Matthew Herper * Ed Silverman Reports E-books Podcasts Tools & Trackers * CRISPR Tracker * Breakthrough Device Tracker * Generative AI Tracker * Obesity Drug Tracker Events * Upcoming Events * Summits * 2025 Breakthrough East * 2025 Breakthrough West Community * STAT Wunderkinds '24 * STAT Madness Video Advertise * STAT Brand Studio Don't miss out Subscribe to STAT+ today, for the best life sciences journalism in the industry Learn more In the Lab Using lab-grown human mini-brains, scientists find links between head trauma, herpes, and Alzheimer's Research suggests concussions could awaken latent infections in the brain and lead to dementia * Manage alerts for this article * Email this article * Share this article Image of a human brain organoid stained with DAPI (teal) and VIPR2 (magenta). -- infectious disease coverage from STAT Image of a human brain organoid.WIkimedia Commons [megan-m-av] By Megan Molteni Jan. 7, 2025 Science Writer At Tufts University in Medford, Mass., researchers loaded a tiny 3D model of the human brain into a plastic shell resting atop a spring-loaded platform. Inside this polymer skull, the donut-shaped ball of living brain tissue floated in a warm, salty bath, its neurons whispering to each other in the darkness. Then a piston struck the platform, whipping it back and forth, and sending the mini-brain sloshing. Days later, as the team assessed the damage, the results were stark. Some of the human brain-like tissue had been housing a latent infection with a herpes virus, the type that causes cold sores. And the impact of the piston -- intended to mimic a concussion -- had woken that virus up. In those tissues, the researchers found lots of inflammation, newly formed plaques of sticky amyloid proteins, and all around them dying neurons -- the signature marks of Alzheimer's disease. Meanwhile, infection-free brain tissues recovered from the concussion with just a bit of lingering inflammation. advertisement Decades of epidemiological data have shown that infections with herpes simplex virus type 1, or HSV-1 can raise the risk of Alzheimer's disease in certain people. So can a history of head injury. The new research, published Tuesday in Science Signaling, is the first to connect the dots between them, and adds to mounting evidence that this most common form of dementia can be caused by an everyday microbe. "It's super exciting work," said Elaine Lim, an assistant professor at UMass Chan Medical School, who studies the role of genetics and the environment in Alzheimer's disease and was not involved in the study. "The group discovered that traumatic brain injury is one of the ways to get inflammation that is able to result in reactivation of HSV-1, and that has a whole bunch of implications." The results suggest that athletes, military personnel, and other people suffering concussions could be triggering the reanimation of latent infections in the brain that can lead to Alzheimer's later in life. More work needs to be done, but the proposed mechanism points to the use of antiviral drugs as a potential early preventive treatment. "The idea is if you have this sort of injury, it can reactivate HSV-1, which is present in most people whether they know it or not," said Dana Cairns, a stem cell biologist at Tufts who led the work. advertisement More than 80% of adults over the age of 60 are estimated to have been infected with HSV-1 at some time in their lives. It's a virus that never really goes away, even after the immune system kicks in and the cold sores disappear. Instead, HSV-1 goes silent, burrowing into neurons and leaving behind copies of its genome with the potential to restart infections when the immune system is weakened. "HSV-1 is highly prevalent, usually in latent (dormant) form, in elderly human brains, and in people carrying a specific genetic factor, APOE4, it confers a strong risk of Alzheimer's," Ruth Itzhaki, a visiting professorial fellow at the University of Oxford and co-author on the paper, told STAT in an email. Related Story [AlzheimerDrugResearch_v2_Illustration_MollyFerguson_061919-768x432] The maddening saga of how an Alzheimer's 'cabal' thwarted progress toward a cure for decades In 1991, Itzhaki discovered HSV-1 in the brains of elderly people who died with Alzheimer's -- the first indication that infectious agents might play a role in the disease. Although she and a few other researchers have long pursued a "microbial theory" of Alzheimer's, for decades their work was pushed to the sidelines by funders and journal editors. As a result, the field has historically focused on the amyloid plaques that build up between neurons and tau tangles that spread inside neurons as the primary driver of the disease. Removing these plaques is the strategy behind recently approved but controversial drugs like Aduhelm, Leqembi, and Kisunla. That is starting to change, with the National Institute on Aging and the Infectious Diseases Society of America inviting scientists to apply for funding to study the role of pathogens in Alzheimer's in recent years. Cairn and Lim are among a crop of young researchers using new tools like the 3D brain-balls to further investigate Itzhaki's ideas. "The field has really accelerated as a result of the brain organoid technologies that began booming about 10 years ago," said Lim, who first began working with lab-grown mini-brains as a postdoc in the Harvard Medical School lab of genetics pioneer George Church. "They have contributed a lot to the ability to be able to test the molecular effects of viruses in the brain." advertisement The donut-shaped model -- which is supported by a silk protein sponge scaffold -- used by the Tufts team was first developed in 2014, in the lab of David Kaplan, a senior author on the paper. In 2020, Cairn and her colleagues showed that if they infected the human brain-like tissue with HSV-1 in the lab, they developed characteristics of Alzheimer's, including clumps of beta-amyloid. Two years later, together with Itzhaki, Cairn found that a dormant version of the virus could be reawakened by another virus -- the one that causes chickenpox and shingles. Varicella zoster virus, or VZV, as it's known, is associated with elevated risks of developing dementia and studies have shown those risks can be reduced by getting a shingles vaccine. The brain-ball work suggested an explanation for how that happened; VZV creates a firestorm of inflammation that reactivates HSV-1, which kickstarts the process of plaque formation and neurodegeneration. The latest work shows that a traumatic brain injury can create the same sort of inflammatory spark. Related Story [nci-vol-2253-300-768x432] New study supports long-dismissed idea: Herpes viruses could play role in Alzheimer's Li-Huei Tsai, a pioneering Alzheimer's researcher at the Massachusetts Institute of Technology, noted that the donut-shaped model used by the Tufts team is different from a traditional organoid model where free-floating neural stem cells differentiate and self-organize into 3D tissue structures that mimic some aspects of the brain. Still, the results convincingly show that physical impacts to the brain-like tissue could reactivate latent HSV-1 and exacerbate Alzheimer's-related features. "These are interesting findings," she said in an email. "However, more validations are necessary, such as using animal models." Lim, whose own team has also found that acute HSV-1 infection leads to Alzheimer's pathology in brain organoids as well as profound changes in gene expression associated with the disease, said that the latest work addresses one of the biggest criticisms of the microbial theory of Alzheimer's: HSV-1's ubiquity. Alzheimer's impacts only about 10% of the population -- if HSV-1 were causing it, why are there so many people who are repositories of the virus but not developing the disease? advertisement "That has been a tricky thing for the field to reconcile," Lim said. "This paper shows that multiple insults that lead to inflammation in the brain can reactivate latent herpes viruses, showing a mechanism for triggering Alzheimer's-like dementia." For both Lim and Cairns, who have looked up to Itzhaki and her perseverance in the face of decades of hostility from the Alzheimer's research establishment, it's gratifying to see the insights generated by the mini-brain models starting to change perceptions about the possibility that common viruses like HSV-1 could cause neurodegenerative disease. "When she was pitching a lot of these ideas in the '90s, she was treated as a heretic," said Cairns. "Viruses have historically been tied to cancer, and that's more of an accepted thing, but this idea that they can really impact neurological outcomes, I think is really gathering a lot of steam at the moment." Alzheimer's, dementia, neurology, research Submit a correction requestReprints 1. [megan-m-av] Megan Molteni 1. 2. Science Writer 1. 2. Megan Molteni reports on discoveries from the frontiers of genomic medicine, neuroscience, and reproductive tech. She joined STAT in 2021 after covering health and science at WIRED. 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