would hsv vaccines make AD rare?

[Fiver]

Makes sense. The dosages range from 500mg once daily to 3g, one way or another. That's a fairly wide range. So getting the dose right at the start probably takes some time and experience.

I'm constantly reminded of the depth of the expertise here. I'm always learning from ya'll. Thanks.

[circular]

Dosing doses and instructions for valacyclovir depend on whether it's for genital herpes (first outbreak, recurrence, or suppression; immunocompromised or not - all have different doses and instructions), cold sores (episodic or suppression), or zoster. Zoster dosing is the same for everyone, with best results if started within 48 hours.

Zoster may also depend on whether it's for acute outbreak for prevention. I don't think there was anything formal to support it, but when a doctor put me on Valacyclovir to help prevent further shingles outbreaks, she used 500 mg, as opposed to the higher dose in acute shingles. I think she based it on the prevention dose for HSV?

[circular]

It's past my bedtime and I'm falling asleep, but I have some information on what herbs are thought to help strengthen the immune system against viruses. If I don't come back with it soon and anyone's interested, just hit me over the head.

[sarahb12]

Ok, just to confound things (because that's what we do), I googled on HSV and cholesterol. Bingo. HSV suspected of causing atherosclerosis.

https://www.nytimes.com/1986/11/18/scie ... eries.html

https://www.sciencedirect.com/science/a ... 2705000512

https://www.ncbi.nlm.nih.gov/pmc/articl ... ool=pubmed

Lysine was part of a Linus Pauling protocol for atherosclerosis. NYTIMES article was 1986.

[Fiver]

A recent news article about herpes and LOAD. https://www.telegraph.co.uk/science/201 ... tist-says/

A brief mention of herpes this recent news article about the struggle to find a treatment. https://www.nytimes.com/2018/11/19/heal ... drugs.html

I haven't read up on how herpes viruses may or may not induce atherosclerosis in humans. But it is well known in chickens. It's called Marek's disease. https://en.wikipedia.org/wiki/Marek%27s_disease

[Julie G]

Ok, just to confound things (because that's what we do), I googled on HSV and cholesterol. Bingo. HSV suspected of causing atherosclerosis.

Here's an interesting paper that dives into the connection between how the viral/pathogen burden correlates with atherosclerosis. Multiple herpes viruses (and other) cause an uptick in lipid metabolism. When combined with the inflammatory effect- not good .

[Fiver]

Thanks Julie. Sure seems like vaccines and/or antivirals would be helpful. I wonder why it doesn't get more attention. There doesn't appear to be any obvious downside.

[Fiver]

Just circling back to this. This article makes a really strong argument.

https://www.frontiersin.org/articles/10 ... 00324/full

Corroboration of a Major Role for Herpes Simplex Virus Type 1 in Alzheimer’s Disease
Ruth F. Itzhaki* Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom

Strong evidence has emerged recently for the concept that herpes simplex virus type 1 (HSV1) is a major risk for Alzheimer’s disease (AD). This concept proposes that latent HSV1 in brain of carriers of the type 4 allele of the apolipoprotein E gene (APOE-ε4) is reactivated intermittently by events such as immunosuppression, peripheral infection, and inflammation, the consequent damage accumulating, and culminating eventually in the development of AD. Population data to investigate this epidemiologically, e.g., to find if subjects treated with antivirals might be protected from developing dementia—are available in Taiwan, from the National Health Insurance Research Database, in which 99.9% of the population has been enrolled. This is being extensively mined for information on microbial infections and disease. Three publications have now appeared describing data on the development of senile dementia (SD), and the treatment of those with marked overt signs of disease caused by varicella zoster virus (VZV), or by HSV. The striking results show that the risk of SD is much greater in those who are HSV-seropositive than in seronegative subjects, and that antiviral treatment causes a dramatic decrease in number of subjects who later develop SD. It should be stressed that these results apply only to those with severe cases of HSV1 or VZV infection, but when considered with the over 150 publications that strongly support an HSV1 role in AD, they greatly justify usage of antiherpes antivirals to treat AD. Three other studies are described which directly relate to HSV1 and AD: they deal respectively with lysosomal changes in HSV1-infected cell cultures, with evidence for a role of human herpes virus type 6 and 7 (HHV6 and HHV7) in AD, and viral effects on host gene expression, and with the antiviral characteristics of beta amyloid (Aβ). Three indirectly relevant studies deal respectively with schizophrenia, relating to antiviral treatment to target HSV1, with the likelihood that HSV1 is a cause of fibromyalgia (FM), and with FM being associated with later development of SD. Studies on the link between epilepsy, AD and herpes simplex encephalitis (HSE) are described also, as are the possible roles of APOE-ε4, HHV6 and HSV1 in epilepsy.

[Rainbow]

Thanks Fiver — this seems really important.

Cited within your study is the Taiwanese study Anti-herpetic Medications and Reduced Risk of Dementia in Patients with Herpes Simplex Virus Infections — a Nationwide, Population-Based Cohort Study in Taiwan: https://link.springer.com/article/10.10 ... 018-0611-x.

Thought the following quote was interesting:

Previous studies have shown that the reactivation of HSV increases the risk for AD [26, 27]. In one study from Taiwan, the seroprevalence rate for HSV-1 infection reached 95.0% for those over 30 years of age, and for HSV-2, the rate was 31.2% for those over 60 years old [49]. Therefore, considering the high prevalence of latent HSV-1 in the population aged over 30, many of the “newly diagnosed” HSV-1 infections may represent reactivation of the virus, with positive immunoglobulin (IG) G and IgM, rather than a newly acquired primary HSV infection (IgG−, IgM+). One study also pointed out that cold sores, or herpes labialis, only occur in 20 to 40% of the population infected by HSV-1, and the other 60 to 80% of subjects might have been infected but not affected, that is, they were not symptomatic [50]. Furthermore, in our study, the adjusted HR was 2.564 for the risk of developing dementia in the HSV infection group, which is very close to the finding of the HR of 2.55 in the risk of developing AD in a previous study [27]. In our study, serology data was not available. Therefore, a future study using HSV serology is needed to confirm the association between re-activation of HSV and the risk of AD.

[Fiver]

So here is my idea, probably full of holes. Just putting it out there for debate.

Hsv viruses insert their DNA sequences into the nuclear genomes of host nerve cells, and hide there. Part of the "hiding" is shutting down some of the cells natural "cleaning" functions. This can be done by enzymes called HDACs (histone deacetylases; which wrap DNA sequences around histone proteins that serve as "cord keepers", and silence some genes.) Some of the genes that are wrapped up and silenced include viral sequences (hiding) those necessary for effective "cleaning", including those necessary for endosomes and lysozomes to take in and destroy AB peptides (often surrounding virus particles captured from outside cells). So, in this hypothesis, the virus can change it's cellular environment to be more favorable. ApoE4s are especially susceptible because the apoe4 gene already tends to stimulate HDACs, encouraging the wrapping and silencing of these genes. They, thus, over-react to hsv infection. Endosomal / lysosomal dysfunction is common on apoe4s even without hsv infection, and can be corrected in cell cultures either by swapping out apoe4 genes with apoe3 genes or with inhibitors of HDACs, called HDACis. Examples of HDACis include valproic aicd, long used to treat migraines and some type of mood disorders. Sulforaphane from broccoli sprouts is also a HDACi. Simply treating someone with HDACis tends to reawaken have infections, causing outbreaks of things like cold sores. But....and here is my crazy, humble suggestion....a combination of an HDACi and viral suppressor like the val/acyclovirs used in some of the previously mentioned studies could both correct apoe4 endo/lyso-some cycling and cleaning while suppressing additional viral outbreaks.

I'm sure I'm either missing some key information here or researchers are already on it, and it is nothing new. My point is that the drugs to do this experiment already exist, are cheap/generic, and have few side effects. The individual experiments seem to have been done, and they seem to work. They just need to be done in combination.

Thanks for letting me get this off my chest.

Maybe this is nothing new. But it's the best lead I've come across in several years of study.

The real goal, of course, would be a vaccine(s) vs. hsv.