The 12th Invest in ME Research Conference June, 2017, Part 2
MEMum presents the second article in a series of three about the recent 12th Invest In ME International Conference (IIMEC12) in London.
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New study found HSV-1 link to Alzheimer's Disease

Discussion in 'Antivirals, Antibiotics and Immune Modulators' started by Gingergrrl, Oct 27, 2014.

  1. Gingergrrl

    Gingergrrl Senior Member

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  2. alex3619

    alex3619 Senior Member

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    This of course raises issues ... this theory is very much like some theories about ME. Indeed, it may be that all sorts of issues are caused by brain infections, and probably not limited just to the herpes family.
     
  3. Gingergrrl

    Gingergrrl Senior Member

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    @alex3619 That is exactly what I thought when I saw the article! Many people with ME have high titers of EBV, VZV, CMV, HHV-6 and all kinds of herpes viruses. The very name of ME implies an inflammation or infection in the brain. If this process through a herpes virus can lead to Alzheimer's then it seems that this same research can be done to see if it leads to ME. This seems like a huge breakthrough and like you said, it is probably other viruses as well as the herpes family although those seem the most insidious to me.

    ETA I am tagging @Jonathan Edwards as I am very curious to hear what Dr. Edwards thinks about this!
     
  4. alex3619

    alex3619 Senior Member

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    This is tentative association for now. It shows that there is cause for future studies looking at possible mechanisms.
     
  5. Gingergrrl

    Gingergrrl Senior Member

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    I know it is tentative, but it got published in a journal so I am hoping this opens up some new research ideas or links for ME/CFS. It seems that herpes viruses are linked in MS and now tentatively in Alzheimer's and other CNS related disorders?

    I feel like there will be a day that as soon as someone gets mono from EBV, they can be given an anti-viral and maybe avoid the future hell of ME/CFS. Or maybe someone with a strong family history of Alzheimer's or early signs will be given an anti-viral?
     
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  6. Hip

    Hip Senior Member

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    I have it on good authority (ie, a Professor in Alzheimer's research told me) that certain influential scientists in the Alzheimer's field take a very dim view of the theory that infections could underpin Alzheimer's, and so always try to block any grant applications for studies into viral causes of Alzheimer's. Thus researchers looking at viral etiologies for Alzheimer's have a very hard time doing their work, due to a major shortage of funding.

    I cannot understand why some scientists seem to find idea of pathogenic infections causing a neurological or mental diseases so difficult to grasp or accept. We know that neurological or mental conditions are increasingly being linked to brain inflammation, and we know that infections can cause inflammation, so here already is one plausible mechanism by which an infection could underpin a neurological or mental illness.

    I found studies going back to 1991 on PubMed detailing the link between herpes simplex and Alzheimer's, so this idea has been around for some time. Studies have also found Alzheimer's is also linked to Chlamydia pneumoniae, and to Helicobacter pylori.

    So there is a good case for further studies on infectious etiologies for Alzheimer's; not to mention studies using potent antivirals to try to treat Alzheimer's.



    Note that with herpes simplex virus and Alzheimer's, I understand that you need to have the APOE-4 form of the APOE gene before you become susceptible, because the APOE-4 allows the herpes virus to enter the brain.

    This genetic component behind the herpes simplex viral ewtiology might explain why there are high concordance rates for Alzheimer's. Concordance rates indicate whether a disease has more of a genetic, or more of an environmental etiology. Environmental etiologies would include infections or toxins. Concordance rates of 100% indicate a purely genetic etiology; concordance rates of 0% indicate a purely environmental etiology; and concordance rates in between 100% and 0% indicate a mixture of genetic and environmental factors in the etiology.

    The concordance rates for Alzheimer's are around 80%, indicating that Alzheimer's etiology is more influenced by genetic factors than environmental factors. However, because APOE gene plays a crucial role in facilitating the herpes simplex virus infective process of the brain, this might explain why explain concordance rates for Alzheimer's are so high, when in fact this disease may be underpinned by infections, at least in some subsets of the disease.
     
    Last edited: Oct 28, 2014
  7. Gingergrrl

    Gingergrrl Senior Member

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    @Hip thanks for explaining all that and it is a shame that so many scientists are closed minded to new ideas and dismiss them so quickly. My grandfather died of Alzheimer's disease but I never knew there could possibly be a viral component.
     
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  8. alex3619

    alex3619 Senior Member

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    [Sarcasm, black hat on] Oh, @Hip, what a cynic, that would never happen in ME research. [End Sarcasm]
     
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  9. Hip

    Hip Senior Member

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    [Sarcasm] Ah yes, in ME/CFS we are so blessed. In our disease, the course of science always did run smoothly. We've never once been blighted by psychosomatic quackery, the bane of so many other neurological research fields. [/Sarcasm]
     
    Last edited: Oct 28, 2014
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  10. Hip

    Hip Senior Member

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    For fans of the Hameroff-Penrose microtubule theory of consciousness (which hypothesizes that consciousness arises from quantum processes occurring within the microtubules found in every neuron and cell):

    Hameroff et al published a paper not so long ago hypothesizing that a degradation in microtubule polymerization and stability leads to the reduction of conscious awareness, memory and cognitive function that is characteristic of Alzheimer's, proposing that microtubules are destabilized as a result of altered intracellular zinc levels (the zinc levels are themselves perturbed by the beta amyloid plaque found in Alzheimer's).

    In the Hameroff-Penrose theory, microtubules are posited to be the fundamental organelles which generate consciousness from quantum processes (the hollow interiors of microtubules are thought to be so well protected from thermal noise that they can successfully host the incredibly delicate quantum waves).

    If this theory of consciousness is true, you might expect consciousness to begin to fail when these microtubules become unstable.

    Tau and MAP2 are two very important proteins that stabilize microtubules in neurons, so if these proteins become defective, this may affect the microtubules. In the above-cited paper, the Hameroff et al propose that altered intracellular zinc levels result in defective tau protein being produced, leading to microtubule instability, when then results in all the problems with consciousness, memory and cognitive function you find in Alzheimer's.

    It's early days yet, but Alzheimer's might turn out to provide evidence for the Hameroff-Penrose theory of consciousness.



    All this might also have some import for ME/CFS: since the brain fog of ME/CFS feels like you have a deficit of consciousness, I was looking to see if anything in the pathophysiology of ME/CFS might perturb microtubule stability, and thereby contribute to the zombie-like state that we know as brain fog.

    Interestingly enough, I found one study which showed ME/CFS patients have higher levels of autoantibodies to the MAP2 protein.

    Another study found the same thing in lupus patients, and noted that lupus patients with anti-MAP2 autoantibodies were more likely to have neuropsychiatric symptoms such as psychosis, seizure, neuropathy, and cerebritis.
     
    Last edited: Oct 29, 2014
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  11. Hip

    Hip Senior Member

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    Going back to the proposed herpes simplex virus etiology for Alzheimer's, I just found these two papers:

    Herpes simplex virus infection causes cellular beta-amyloid accumulation and secretase upregulation

    Herpes simplex virus type I induces the accumulation of intracellular β-amyloid in autophagic compartments and the inhibition of the non-amyloidogenic pathway in human neuroblastoma cells

    So now we can see a potential causal mechanism for Alzheimer's from beginning to end, by combining these herpes–beta amyloid studies with the Hameroff et al paper :


    Hypothesized Alzheimer's Etiology:

    Herpes simplex virus infection of the brain

    Causes beta amyloid plaque formation

    Leading to altered intracellular zinc levels

    Which creates of defective tau protein

    Causing in microtubule instability

    Resulting in problems with consciousness,
    memory and cognitive function

     
    Last edited: Oct 28, 2014
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  12. Wally

    Wally Senior Member

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    It sure would be nice if the U.S. Government's $40 million Brain Initiative would take a closer look to see if the decades long trail of breadcrumbs left by herpesviruses in the brain might need a second look with today's technology.

    These two articles regarding Alzheimer's and herpesviruses date back to 1982 and 1997.

    1) http://www.ncbi.nlm.nih.gov/pubmed/7116237

    "Can J Neurol Sci. 1982 Aug;9(3):303-6.
    "Limbic predilection in Alzheimer dementia: is reactivated herpesvirus involved?".
    Ball MJ.
    Abstract

    In the brains of patients with senile dementia of the Alzheimer type (SDAT), the quantitatively pathognomonic neuronal lesions (tangles, plaques, granulovacuolar degeneration, Hirano bodies, and nerve cell loss) are predisposed to occur especially within the limbic system. Anatomical and physiological studies indicate that fibres from the trigeminal ganglia innervate meninges and vessels within the middle and anterior cranial fossae, especially in the same subfrontal and mesial temporal regions preferentially afflicted in acute herpes encephalitis. These limbic regions are critical for normal memory processing and recall. Explantation and cocultivation techniques have recently demonstrated Herpes simplex virus in many humans trigeminal ganglia, which also reveal a life-long lymphocytic infiltration in the absence of any pathological changes in the sensory neurones. These lymphocytes may represent a histological marker of latent herpes virus, which when reactivating is well-established as the ganglionic source of recurrent herpes labialis. It is suggested that reactivation of the same dormant viral material travelling centripetally instead might be the cause of the "degenerative" lesions typical both of Alzheimer's Disease and of the normal aged human brain.

    PMID:
    7116237
    [PubMed - indexed for MEDLINE]"

    2) http://www.ncbi.nlm.nih.gov/pubmed/9020387

    "Clin Neuropathol. 1997 Jan-Feb;16(1):1-12.
    Neocortical temporal lobe sclerosis masquerading as Alzheimer dementia: does herpes virus encephalopathy protect against Alzheimer's disease?
    Ball MJ1, Kaye JA, Steiner I.
    Author information
    Abstract

    Semi-quantitative neuropathological analysis and morphometric evaluations of the brains of 5 elderly people (63-85 years old) dying following a 5-27-year history of dementia reveal that, despite exhaustive survey of all major brain regions, 4 of these cases show virtually no histopathological lesions of Alzheimer's disease. Instead their CNS manifests a severe, bilateral, neuronal depletion, and astrogliosis afflicting the lateral temporal neocortex, highly compatible with a previous herpetic viral encephalitis. In the fifth case unilateral neocortical temporal lobe sclerosis is accompanied by Alzheimer's disease, but with much more dense Alzheimer lesions throughout the contralateral cerebral hemisphere. Three of these 5 individuals had a history either of herpes zoster of the skin or of a single episode of viral meningoencephalitis, roughly concomitant with the onset of memory loss. This clinical and pathological evidence that a remote herpes virus encephalopathy (when bilateral) "protects" that brain against Alzheimer's disease strengthens our growing suspicion that incomplete replication cycles of herpes simplex or zoster virus, following repeated reactivation within neurons of the trigeminal ganglia, may link these viruses to the pathogenetic cascade underlying dementia of the Alzheimer type.

    PMID:
    9020387
    [PubMed - indexed for MEDLINE]"
     
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