Could getting a cold sore increase risk of Alzheimer’s?

By Eloise Mikkonen

close up. beautiful lips virus infected herpes

Herpes in the brain?

On the back of a very successful (at least on the scientific side of things) year in research, I’ve recently had another article published. Not as fanciful as beer staving off Alzheimer’s disease, but something that has been popping up on news sites all over the world over the past couple of years. That is, an infectious agent causing Alzheimer’s disease – namely the Herpes simplex virus (HSV). HSV1 (type 1) generally causes the common coldsore that appears on your face, most often your lips. Another type of the same virus (HSV2) is known to cause genital herpes. Approximately 80-90% of the population are affected with HSV1, and once you get it, it doesn’t go away (it just hides in your nerve cells).

I got interested in this topic a few years back when I came across a paper that showed amyloid beta (Aβ) aggregations (the sticky clumps of protein known as senile plaques that are thought to be a major cause of Alzheimer’s disease) were clumped together at the same location in brain tissue as HSV. Now this doesn’t really answer the question of cause or effect, so I thought I could look at this virus in my brain tissue samples and perhaps be able to see what would come first – virus or brain lesions.

After teaming up with some researchers at Umeå University in Sweden, who have a good detection system set up for analysing HSV, we moved ahead and analysed whether we could find HSV in the TASTY series (one of the brain collections I use). We had 584 individuals’ brain tissue for analysis and found 11 (1.9%) that were positive for HSV in the brain. Of those 11, 6 had Aβ aggregations (~55%). There were also a large proportion of individuals that didn’t have HSV in the brain, but did have brain lesions (160 cases, ~30%).

HSV first infection is usually in childhood, and the youngest age of the cases with HSV in the brain was 43, so this suggests that it happens later on. At least it’s after the initial plaques that appear in the brain (around 30 years). It doesn’t completely discredit the idea that HSV could cause AD, but the fact that so many individuals (160) had brain lesions but no HSV in the brain, suggests something else causes the brain lesions. Although HSV could potentially make things worse. Because we had so few cases with HSV in brain, we can’t really make any assessments on when it is likely to enter the brain – that’s something for our future research! Of course our previous work has shown that the brain lesions already appear around age 30, suggesting that if these are the cause of the disease, it’s starting quite a lot earlier than previously thought. This then strongly suggests that the development of brain lesions is caused by something else, not HSV.

The most significant finding of our study was that there were individuals that had HSV in their brains. That they weren’t suffering from the rare deadly brain infection known as Herpes simplex encephalitis (HSE). They had no symptoms that would suggest HSV was present in their brain tissue. This study was the largest of its kind showing HSV can get into the brain without showing symptoms. Our next step will be to identify exactly which brain region it is found in, and map the potential route for entrance by HSV. It will also be important to identify what triggers the ability of HSV to gain access to the brain of some people, but not others?

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As age increases, you can see a decrease in the percentage of those without brain lesions (No neuropathology, clear bars), and a corresponding increase in those with senile plaques (Aβ aggregations, light grey shaded bars), tangles (NFT, darker grey shaded bars), both combined brain lesions (Aβ & NFT, darker patterned grey bars), Alzheimer’s disease (AD, solid line) and HSV in the brain (HSV DNA positivity, dashed line).

Compared to other studies investigating Alzheimer’s disease patients and controls, which numbered generally under 50 individuals, our study found a very low incidence of HSV in brain tissue. Other studies suggest anywhere from 20 up to 100% of controls (that is non-demented people) have HSV in the brain. It might be that our study criteria was too strict, but even if we included all slightly positive cases, that only equates to a 6% incidence. It is perhaps more likely that our samples are quite old, and were not ‘fresh frozen’ tissues, so we will also perform a similar study on a newer autopsy cohort collected here at the University of Tampere.

So at least for now, you can rest easy that HSV probably isn’t going to cause you to get Alzheimer’s disease. At least that makes me feel better considering during the study and preparation of this manuscript I had about 6 outbreaks of coldsores!!! The paper was published as open access, meaning you can read the whole pdf of the article here: http://dmm.biologists.org/content/9/11/1349

Enjoy!

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