Herpes Simplex Virus-1 and Alzheimers

Abbie, you ROCK!!!

Thanks for blogging!

Educate me: correlation/causation?

You're like oh, HSV-1 must be eating your brain and pooping plaque.

But I'm like, well maybe HSV-1 eats this plaque for breakfast, just not quick enough to keep you from getting Alzheimers?

It's an interesting start, but as abbie, whom i worship, pointed out, with the prevalence of HSV1 being so high, it's going to be hard to dig out causation without a lot more data.

I'd think the first study I'd want to see is some study about how many people with herpes end up with Alzheimers. Of course that'd take some time. In the meantime trying to find out how many current Alzheimers have herpes somewhere versus a wider sample would be interesting. It may just be that Alzheimers (or whatever causes it) make one prone to get the virus (or spread it within your body).

So, I read the abstract, but that's it since I don't have a subscription. Also, I'm not a physiologist or virologist (as you can probably guess from my lack of subscription if not from all any misinterpretations that I might provide). However, just reading the abstract it seems that there are 3 lines of evidence here: 1) correlation between Alzheimer's and HSV-1 (in people with the type 4 allele of the apolipoprotein E gene); 2) experimental induction of beta amyloid (plaque gunk) in mouse brains and cell lines by HSV-1 infection; and 3) strong association between HSV-1 DNA in effected tissues (reported in this study). At least one of the lines of evidence is experimental rather than just correlational. It seems that the authors conclude that HSV-1 infection plays a causal role (and may be a necessary cause??) but it is not, on it's own, a sufficient cause.

Given the percentage of people who have herpes and the fact that you can't get rid of it, what about how many people who end up with Alzheimers who never had herpes? Also, what about all those other forms of herpes; chicken pox, shingles, etc? Has anyone looked into other possible variants (not-quite-Alzheimers-diseases)? Just curious; no herpes here.

I don't know a lot about neurobiology, and I may be about to say something stupid. But does this really demonstrate a link between the virus and Alzheimer's disease? I mean, perhaps the amyloid plaques are just an environment that the virus loves? Perhaps more Alzheimer brains should be cut up (I know, they don't grow on trees...), in order to see whether the virus is really always present in the plaques? 6 cases is not a lot...

MattK, you're right. Their in vitro and mouse work was published in Neuroscience Letters in 2007 (doi:10.1016/j.neulet.2007.09.077). They also found that levels of the enzymes responsible for beta-amyloid production also increased following HSV1 infection.

What excites me about this work is that it is as far as I'm aware the first time that a plausible trigger for the chain of events leading to the development of amyloid plaques has been identified. Interestingly they also mention an earlier study by another group which found amyloid plaques in the brains of mice infected with Chlamydia pneumoniae, so it's possible that HSV1 is not the only infectious agent that can trigger the onset of Alzheimers.

What I'm wondering is how early will treatment to eradicate HSV1 infection need to be started to prevent or stop the development of Alzheimers. I suspect that other treatments that remove plaques and tangles will still be required in many cases.

DO NOT SPAZ!

As someone with cerebral palsey, can I go through motions of objecting to this expression? I've long ago given up expecting to influence anybody, but it gives me something to do.

@chris y: is spaz a reference to spasticity then? I had assumed it was an abreviation of spasm.

Apparently I was being naive...

manigen, the word "spastic" is derived from "spasm", and was originally applied medically as a straightforward description of the symptoms of cerebral palsy. "Spaz" is a common abbreviation, used interchangeably with the full word as an insult to mean weak or uncontrolled. The verb derived from the noun.

Like I say, disabled people aren't a sexy minority, and I long ago gave up expecting "progressive" people to extend me the same linguistic courtesy they give to women, LGBT people and racial minorities. Nowadays I just mention it once in a while for shits and giggles.

"I repeat, HSV-1 people, DO NOT SPAZ! There is still a ton of research to do"

So you're saying that there's no simplex answer to this problem?!

Yeah, ok, but...I'm still freaking out a little.

How do you get HSV-1, again?

Dang, hit post too soon. A question I meant to ask:

I get moderately frequent cold sore outbreaks. Years ago I had a scrip for Zovirax, which didn't seem to help much (though it was hard to take with the proper regimen). Eventually I gave up on it. About a year ago I went back to a doc to see what other options were available, and he gave me Valtrex (not regular use, just for when it flares up...thank Dog given the insane price!). I think it may work better, but here's the thing that prompts my question: Since I started taking this, it seems like the lip sores have migrated to my mouth (base of the tongue canker sores). I've never had this pattern of expression before. Could the drug cause this? How?

Don't even go there, WW. You'll lose.

How do you get HSV-1, again?

Kissing. Obviously, you're not at risk.

"How do you get HSV-1, again?"

Kissing, sometimes from family members during childhood. I got my first cold sore out of the blue at like age 8.

Thanks, Abbie, for speaking some sense about this. This reminds me of the crap that came out when aluminium was found in the plaques too. What, you mean the most common metal on the planet, that's basically in everything you eat, was found in your brain tissue? GET OUT!

rrt, I can only speak from my experience and those of friends. When I first got infected, my outbreaks were frequent and painful. Ten years later, I almost never get cold sores.

I have had friends, however, who started only with sores on the lips, and then after a few years got them inside the mouth and even in the nose (ouchie!). We all used the same medication (Zovirax), so I can only suggest that our immune systems dealt with the virus with different degrees of effectiveness? Hope yours settle down soon.

Yeah, it's Herpes B you need to worry about.

There are a few problems with this hypothesis. Amyloid builds up in many tissues, not just the brain. Normally amyloid doesnt accumulate because the removal pathways remove it faster than it can build up. Those removal pathways include the proteasome (for small pieces of junk) and autophagy for large pieces. Autophagy also happens to be the way that DNA from dead cells gets removed. If you inhibit autophagy, you cause the accumulation of protein aggregates including amyloid.

Brains with fewer plaques have the same (or higher) HSV-1 DNA content but have a smaller fraction of the total brain HSV-1. That would make sense if all they are seeing is that the amyloid plaques have more partially degraded DNA because what ever is inhibiting the degradation of amyloid (and so is allowing it to accumulate) is also inhibiting the degradation of DNA from dead cells.

I bet that if you looked for other DNA, such as from endogenous retroviruses, you would find more of it in those plaques too.

I bet you would find more junk of all sorts. Everything that doesnt get cleared by autophagy will accumulate to higher levels. I bet you would be able to find any virus that persists, including chicken pox.

Paul, there was a study that removed amyloid plaque via vaccination. The technique worked in that it removed plaque, but it had no effect on the progression of dementia. The "problem" of Alzheimer's is upstream of the formation of plaque. Plaque is an effect, not a cause.

I just read of a spanish company that are claiming to have a vaccine for alzheimers, made from chicken polyclonal antibodies. Claim trials in dogs show effectiveness.

It seems to me they think alz is caused by one or more viruses, as discussed here, and are using a scattergun approach. A more modern wart-puss treatment?