would hsv vaccines make AD rare?

[Gillyp]

A warm welcome to our community, Jayredliner. Thank you so much for posting these links related to antivirals and AD and for taking the time to write a summary for us. This is a very relevant topic and it's certainly important research that will hopefully benefit many. I look forward to reading future posts from you. You obviously love learning and passing on that information to others.

There's a ton of helpful information and reference studies on our site so I hope you'll take the time to look around. The best place to start is our very comprehensive Primer (viewtopic.php?f=33&t=1418). The Wiki is also worth referencing (https://wiki.apoe4.info/wiki/%22How-To% ... fo_website) and using the search function will help you quickly find any information you may be looking for. When and if you feel like sharing your own story we'd love you to post. Our Stories is a the perfect forum to do that. Once again, welcome.

[CarrieS]

Here's another story, posted today showing even more mounting evidence: http://www.bbc.com/future/story/2018102 ... alzheimers

Thank you for posting this link jayredliner. I too would like to welcome you to the community and look forward to reading more of your contributions!

[circular]

This is a fine, recent review of where this research stands, also by Ruth F. Itzhaki but much more comprehensive than the last link. antimatter37 posted it in this herpes thread.

Corroboration of a Major Role for Herpes Simplex Virus Type 1 in Alzheimer’s Disease

In addition to asserting that the extensive Taiwan data establishes both causation and potential prevention, since HSV+ who were treated with antivirals didn't progress to AD (relatively speaking) -- also suggests links with herpes zoster, especially the opthalmic manifestion of it (being so close to the brain), as well as epilepsy, fibromyalgia, and oral bacterial infections.

Here's what the paper says about herpes zoster (shingles):

Two of the articles investigated varicella zoster virus (VZV) infection in relation to long-term neurocognitive changes and the development of dementia. VZV causes chicken pox, but after acute infection it remains in the body lifelong in latent form, and in some people in older age it reactivates, causing shingles, which both sets of authors referred to as herpes zoster (HZ) and the virus as HZV. The first article, by Tsai et al. (2017), investigated 846 patients (mean age 62.2 years) who were diagnosed with HZ ophthalmicus (HZO) in 2005 and who developed dementia in the following 5 years. The development of dementia was compared with that of an age-matched control group of 2,538 subjects during the same 5-year period. The percentage of patients with HZO who developed SD was 4.16%, whereas that of the controls was only 1.65% (P < 0.001), and the crude hazard ratio of developing SD within 5 years of HZO diagnosis was calculated to be 2.97 after adjustment for patients’ characteristics and co-morbidities. This represents a remarkably high risk of developing dementia amongst HZO sufferers.

In the second article, by Chen et al. (2018), 39,205 patients with HZV, age range 54–90, were diagnosed during the period 1997–2013 and were followed over an average period of 6.2 years. The incidence of dementia was compared with that of 39,205 controls (mean age of both groups was 63.5 years). The hazard ratio was only very small, namely, 1.11. A possible explanation for this marked difference from the HZO results is that in HZO the virus is more likely to enter the brain and cause damage there than in HZV infection. However, HZ patients who were treated with antiherpes antivirals—acyclovir, valacyclovir, tromantadine, famciclovir—showed a dramatic decrease in incidence of dementia to about a half of that in the untreated group, adjusted HR, 0.55; 95% CI, 0.40–0.77, (P < 0.0001). [Emphases added]

In the past I looked into whether I should have shingles vaccines since I had my first outbreak in my 40s. It seemed clear that the vaccine could help prevent additional outbreaks, and if you got shingles again anyway, it would not be as severe. I did get shingles again after the (old) vaccine. It was milder than the first episode. I plan to get the newer shingles vaccine and go back on, and stay on, Valacyclovir. I had only stopped it because my new insurance didn't cover it But I'm not clear, in the studies when they say patients were 'treated' with antivirals and had reduced incidence of AD, do they just mean the treatment at the time of the acute episode, or did the patients stay on antivirals to prevent recurrence? I'm pretty sure I took antivirals both times I had shingles, but I've also had the impression they could help prevent recurrences, so continued use, since established and safe, might be warranted.

[SusanJ]

But I'm not clear, in the studies when they say patients were 'treated' with antivirals and had reduced incidence of AD, do they just mean the treatment at the time of the acute episode, or did the patients stay on antivirals to prevent recurrence?

Wondering the same thing, Circ. Treat the outbreak or go on some long-term antiviral use. I've had one mild shingles episode, but did not take any antivirals (RATS!).

[Chameleon]

Hi jayredliner!

Welcome to the APOE4 community! I thought the research paper as well as the article you posted were both very interesting. The whole idea that antivirals and a HSV vaccine could be helpful is certainly encouraging. I know many of my clients do have the Herpes virus so anecdotally there seems to be a link there.

If you haven't done so already, feel free to explore the Primer because it contains a ton of information. And the Wiki is also very useful.

Many members also tell their story in the Our Stories forum so please feel free to share more of your background with us.

Looking forward to hearing more from you!

[Fiver]

This seems helpful. And possible. I should probably feel good about that. But it would really be nice to have a way to measure any potential benefit....now that would be great!

[circular]

But I'm not clear, in the studies when they say patients were 'treated' with antivirals and had reduced incidence of AD, do they just mean the treatment at the time of the acute episode, or did the patients stay on antivirals to prevent recurrence?

Wondering the same thing, Circ. Treat the outbreak or go on some long-term antiviral use. I've had one mild shingles episode, but did not take any antivirals (RATS!).

In wonder if the Taiwan paper holds any clues to whether just treating during an acute flare works. I strongly suspect this was the case and that there wasn’t a substantial enough proportion of apoe4 HSV+ Taiwanese who were treated with antivirals over the long term to determine causation from. I think ongoing use of an antiviral may help prevent flares which would be valuable, but I don’t know if when it’s said they are safe if they’ve only been studied in short term, acute use.

[jayredliner]

But I'm not clear, in the studies when they say patients were 'treated' with antivirals and had reduced incidence of AD, do they just mean the treatment at the time of the acute episode, or did the patients stay on antivirals to prevent recurrence?

Wondering the same thing, Circ. Treat the outbreak or go on some long-term antiviral use. I've had one mild shingles episode, but did not take any antivirals (RATS!).

I believe this has been addressed.

Harris, S. A., & Harris, E. A. (2018). Molecular Mechanisms for Herpes Simplex Virus Type 1 Pathogenesis in Alzheimer’s Disease. Directory of Open Access Journals, 10, 48-99.

"Harris & Harris, (2018) proclaim neurofibrillary tangles, amyloid beta (Aβ) and P-tau plaques are the “hallmark” of AD infected brains. Citing previous research (Ho et al., 2005), Harris & Harris (2018), detail how AD brains are often inflamed with these plaques, which are likely caused by the body’s own macrophage response to invaders like HSV-1. Harris & Harris (2018), discuss research by Alvarez et al. (2012) which demonstrated that the combination of these plaques and the body’s response cause neural damage and cell death, however, those changes are not seen when treated with the antiviral drug acyclovir (ACV)."

In essence, I believe this is saying that the replication of the viral DNA is causing the accumulation of Aβ and P-tau, not the initial infection. I think this has been confirmed with another study, although the name of that study escapes me right now.

[Fiver]

interesting read. thanks!

[Fiver]

related....

Active HHV-6 Infection of Cerebellar Purkinje Cells in Mood Disorders

Early-life infections and associated neuroinflammation is incriminated in the pathogenesis of various mood disorders. Infection with human roseoloviruses, HHV-6A and HHV-6B, allows viral latency in the central nervous system and other tissues, which can later be activated causing cognitive and behavioral disturbances. Hence, this study was designed to evaluate possible association of HHV-6A and HHV-6B activation with three different groups of psychiatric patients. DNA qPCR, immunofluorescence and FISH studies were carried out in post-mortem posterior cerebellum from 50 cases each of bipolar disorder (BPD), schizophrenia, 15 major depressive disorder (MDD) and 50 appropriate control samples obtained from two well-known brain collections (Stanley Medical Research Institute). HHV-6A and HHV-6B late proteins (indicating active infection) and viral DNA were detected more frequently (p < 0.001 for each virus) in human cerebellum in MDD and BPD relative to controls. These roseolovirus proteins and DNA were found less frequently in schizophrenia cases. Active HHV-6A and HHV-6B infection in cerebellar Purkinje cells were detected frequently in BPD and MDD cases. Furthermore, we found a significant association of HHV-6A infection with reduced Purkinje cell size, suggesting virus-mediated abnormal Purkinje cell function in these disorders. Finally, gene expression analysis of cerebellar tissue revealed changes in pathways reflecting an inflammatory response possibly to HHV-6A infection. Our results provide molecular evidence to support a role for active HHV-6A and HHV-6B infection in BPD and MDD.

https://www.frontiersin.org/articles/10 ... on-bipolar