Can you “catch” Alzheimer’s?: AD and the shingles connection

For years I’ve encouraged my patients to get the Shingrix two-shot vaccination to protect against Herpes zoster, or shingles, but with no particular enthusiasm. I hadn’t even gotten it myself. I could measure the levels of antibodies that tamp down the Varicella-zoster (VZV) virus, in my patients and in me, to assure myself they were sufficiently high. And, frankly, I was in no hurry to get a vaccine that, for a day or two, would likely leave my shoulder feeling sore and me flu-ish.

That was then.

This past October Nature Medicine published a remarkable study by an international research team, “Varicella-zoster virus reactivation and the risk of dementia,” which makes a convincing case that the Shingrix vaccine also protects against Alzheimer’s disease. I was surprised but perhaps I shouldn’t have been.

The old dogma that the only effective way to fight AD was to develop drugs that reduced or eliminated the amyloid protein plaque and tau tangles, hallmarks of the disease, has been largely discredited -- we still have no truly safe and effective drugs to show for it. But over the past year or so, we’ve amassed evidence that familiar, but very different, molecules can significantly reduce the incidence of AD, stopping the horse before it leaves the barn, before these toxic proteins have had a chance to clump inside the neurons.

As I’ve discussed in previous blog posts, ezetimibe  (brand-name Zetia), lithium and, yes, psilocybin look to reduce the neuroinflammation that drives AD. One important mechanism here is likely the upregulation of the enzyme telomerase which reduces the rate of telomere attrition and looks to reduce systemic inflammation. (Longer telomeres, protective caps at the end of their chromosomes, means our oft-dividing cells, most crucially in the immune system, are able to keep on dividing and not become senescent and not generate inflammatory cytokines.) The recombinant zoster vaccine (marketed as Shingrix) seems different in kind from these three drugs since it’s protecting us from a threat that comes from outside the body. But it’s addressing the same problem of inflammation from a different angle.

By charging up the immune system’s CD4 T cells that keep the VZV virus in check, the vaccine helps prevent the latent virus (which we carry if we had chicken pox as children) from replicating to such a degree that we experience shingles symptoms. (Make no mistake, shingles is bad news, not only the painful rash that may last for weeks, but also the possibility of more severe longer-term nerve damage like post-herpetic neuralgia.) And that sidestepping of shingles confers an inflammation-reduction benefit. Our T cells don’t have to turn over as frequently in order to fight the outbreak, thus delaying or preventing cell senescence and the attendant inflammation, in the case of AD, neuroinflammation.

But as the Nature Medicine paper makes clear, from an AD prevention perspective, the vaccine may be even more valuable in limiting silent “sub-clinical activation” of the latent virus. When we’re stressed, either psychologically or physically, our immune system response is suppressed, allowing “viral load” to increase. (Most of us carry the HSV-1 virus, another member of the herpesvirus family, and we’re familiar with the cold sores that sometimes pop up when we’re feeling stressed.) Even though most of us won’t contract shingles over the course of our lifetimes, our immune systems may be regularly fighting upticks in the VZV viral load, insufficient to cause shingles symptoms but cumulatively, quite enough to over-stress the immune system, giving rise to, once again, cell senescence and potentially neuro-toxic inflammation. (My relatively high antibody levels may well be protecting me from shingles but they could also be a sign of a chronically overactivated immune system.)

So, the line we’re drawing from viral infection to inflammation to increased AD risk is exciting, but where’s the proof? The Nature Medicine study researchers convincingly tied together different strands of evidence. They followed over 100 million U.S. adults fifty and over and found a consistent relationship between VZV reactivation (manifested as shingles outbreaks) and increased dementia risk and, conversely, between the herpes zoster vaccination and reduced dementia risk. For instance, people who had recurrent shingles outbreaks had a 7-9% higher dementia risk over a 3-9-year period. Earlier research had shown that today’s recombinant double-dose Shingrix vaccine provided 17% more dementia-free time over six years than the live attenuated virus vaccine it supplanted--- 164 more days without dementia. Another analysis of the data found that adults just above the shingles vaccine cut-off age of 50 had a 20% lower incidence of dementia than those who fell just below the age cut-off.

Maybe more interesting to me was the experimental work. The researchers infected human neural stem cells in vitro with the Herpes simplex virus (HSV-1) and saw those cells develop amyloid plaque and tau protein tangles, markers of AD. They didn’t see the same thing when they infected the cells with VZV alone. This suggests that the reactivation of VZV can trigger a similar reactivation of HSV-1 which, in turn, may directly promote those pathological brain changes. (Sometimes a cold sore is not just a cold sore. In light of the HSV-1-AD connection, it makes sense to take the oral antiviral Valtrex at the first sign of a cold sore or a genital sore – caused by yet another herpesvirus – or, if you’re prone to frequent outbreaks, take it daily for viral suppression.) 

So, we see a picture emerging. Most of us carry the VZV virus, most commonly in its latent “sleeping” form, in the neural ganglia and outside the brain proper. Under the right conditions (think stress) the virus can escape into the neurons and the blood stream causing damage inside the brain and elsewhere. The Nature Medicine study only concerned itself with establishing a VZV-AD connection. But there could well be, for instance, a link with cardiovascular disease, another age-related condition driven by inflammation.

A healthy lifestyle – think good sleep, good exercise, good diet – affords considerable protection against Alzheimer’s. But for people fifty and over, especially for those, like me, who carry the APOE4 genetic variation which increases AD risk, the Shingrix vaccine is a low-risk, high-upside, no-brainer. And yes, I’m now willing to tolerate that under-the-weather feeling, and the sore shoulder, for a day oxr two. Happily. 

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Polisky, V., Littmann, M., Triastcyn, A. et al. Varicella-zoster virus reactivation and the risk of dementia. Nat Med (2025). https://doi.org/10.1038/s41591-025-03972-5

Khokale R, Kang A, Buchanan-Peart KAR, Nelson ML, Awolumate OJ, Cancarevic I. Alzheimer’s Gone Viral: Could Herpes Simplex Virus Type-1 Be Stealing Your Memories? Cureus. 2020;12(11):e11726. doi:10.7759/cureus.11726