Could a Virus Trigger Alzheimer's Disease?

But Itzhaki kept digging. A huge leap forward came in 2007 when she and colleagues infected human brain cells with HSV-1 and later saw beta-amyloid proteins clumped together, a hallmark of Alzheimer’s disease.

In 2009, she reported finding HSV-1 within amyloid plaques in human brains. And in 2011, she showed that adding antiviral drugs to HSV-1–infected cells from monkey kidneys, which contain the proteins implicated in Alzheimer’s, reduced the clustering of amyloid as well as tau. About a decade earlier, Itzhaki had begun suggesting vaccination against HSV-1 as a prevention possibility. Vaccines against some herpesviruses exist, but not for HSV-1.

Her research — and work by others that followed — suggested that beta-amyloid might be an immune defense to trap and get rid of the viral invader, Fülöp says. The viral hypothesis started to gain more supporters.

How could a virus lead to Alzheimer’s disease?

Researchers suspect HSV-1 gets into the brain during middle or late life, Itzhaki says. After lying dormant for years in nerve cell bundles outside of the brain — which many herpesviruses, including the one that causes chicken pox and, later, shingles, are known to do — HSV-1 may reawaken and travel along nerves to the brain.

HSV-1 may trigger certain brain cells called glia to kick off an immune response in the brain. That response involves instructing nerve cells to make extra amyloid-beta, which engulfs and disarms the virus. The problem occurs if the brain can’t clear out the extra amyloid, leading to a toxic cycle that keeps inflammation at cell-damaging levels.   

A similar process may pull tau into the problematic mix. Research published in 2025 in Cell Reports suggests that upon detecting HSV-1, the immune system triggers a boost in tau production and changes how that protein functions. In the study, the altered tau led to fewer signs of HSV-1 inside rat nerve cells and boosted cell survival. It hints that building an army of altered tau might help defend the brain from pathogens in the short term, but may cause damage if the brain continues the higher tau production to keep fending off ever-present HSV-1.

Most researchers assume that a buildup of altered tau, which is seen in Alzheimer’s disease, is always toxic, says neuroscientist and bioengineer Or Shemesh, assistant professor at the Hebrew University of Jerusalem and coauthor the 2025 paper. He proposes that a small amount might be beneficial as an immune defense in the brain. But the tau tangles seen in brains with Alzheimer’s disease could be a sign that the initially helpful mechanism “got out of hand.”

More viruses and other microbes may be involved

While most work on viruses and dementia has focused on HSV-1, scientists suspect this pathogen is not the only instigator. Studies have suggested ties with other herpesviruses, such as HSV-2, which can cause genital herpes, and cytomegalovirus, which can lead to mononucleosis, sometimes called the “kissing disease.” Even bacteria that cause Lyme disease and gum disease are under investigation.

A connection between a virus and neurological disease isn’t unheard of. Epstein-Barr virus, another herpesvirus that causes mono, has been linked to later development of multiple sclerosis, in which the body’s immune system attacks the protective covering of nerve cells in the brain and spinal cord.

But not everyone infected with HSV-1 will develop Alzheimer’s disease, which has made the hypothesis difficult for many researchers to accept, Fülöp says. Most people carry the common virus, but only about 11 percent of people 65 and older have Alzheimer’s disease. Even the minority who develop cold sores from HSV-1 are not automatically destined for a future with this form of dementia, Shemesh says.

“We all have [pathogens] in our brains, or some subsets of them,” he says. “So why [does] one person get Alzheimer’s and another person get nothing?” The difference, he suspects, is “how our immune systems, in the brain and outside the brain, react to the viruses.”

Maybe an environmental trigger

Still, many researchers doubt that a virus can cause Alzheimer’s disease. Instead, a pathogen may contribute to developing the disease by exposing other weaknesses rooted in genetics, such as an immune system unable to properly do its job or that puts up too many defenses, says neurologist Lennart Mucke, M.D., director of the Gladstone Institute of Neurological Disease in San Francisco.   

“If an abnormal immune system … is the risk factor for Alzheimer’s disease, the infection allows the abnormal immunity to play out because it challenges the immune system,” he says. Rather than being a key driver of Alzheimer’s disease, pathogens may act as “environmental triggers that interact with many genetic risk factors and bring those out.”

Although Mucke questions the virus hypothesis, he’s eager to see the results of a clinical trial investigating whether an antiviral drug, which stops an existing infection, can slow disease progression in people with mild Alzheimer’s disease and HSV-1 or HSV-2. The study was completed in September 2024, and researchers plan to report the results in a few months. “There’s enough evidence of associations here that it is worth putting this to the test,” Mucke says. “When there are promising or potentially interesting links, they certainly deserve to be tested in well-controlled trials.”

Regardless of the trial’s outcome, researchers who spoke to AARP agree that vaccines may help stave off Alzheimer’s disease in some capacity. “The most powerful prevention that we can really advise … [is] to be vaccinated for not only viruses, but any vaccine-preventable disease,” Fülöp says.