. Herpes simplex infection and the risk of Alzheimer's disease-A nested case-control study. Alzheimers Dement. 2014 Oct 7; PubMed.


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  1. I agree with Brian Balin's comment on Madolyn Bowman Rogers' article about the intriguing effect of the Borna disease virus X protein, and would add only that it is in the interest of Borna and other viruses not to kill cells as in doing so, the virus too would succumb. In the case of HSV1, entering a state of latency in the host is a means of survival, providing a permanent reservoir of virus, despite frequent reactivations leading to productive infection and cell death.

    On the theme of a viral role in AD, It is worth stressing that there are now some 80 papers by several groups (including those by Lovheim and colleagues), including 40 from mine, that directly or indirectly support the role of HSV1 in AD. These are striking in their use of remarkably diverse approaches—epidemiological, virological, genetic, and cell biological. My recent review (Itzhaki, 2014) summarizes them and explains certain relevant concepts in the hope that they will be better understood by those in the AD field who oppose a viral role. In fact, opposition to a role of HSV1 in AD has been expressed in a mere two publications, 11 and 13 years ago, in which the authors described their inability to detect HSV1 DNA in elderly and AD brains; however, six papers by groups other than mine have detected HSV1 DNA in such brains.  

    As for treating AD with antivirals with the aim of reducing disease progression, studies on three antivirals that act by different mechanisms have recently been published by my group (Wozniak et al., 2011; Wozniak and Itzhaki, 2013; Wozniak et al. 2013). Each antiviral was found to reduce substantially the accumulation of Aβ and phospho-tau that occurs in HSV1-infected cell cultures. The antiviral most likely to be used for therapy, acyclovir (or in practice its biodrug, valacyclovir), is very safe, and has the great advantage over many other treatments for AD that it targets only infected cells. Also, it should reduce or stop all viral damage, including the accumulation of Aβ and p-tau, irrespective of whether they are actual causes of the disease. There have been 413 AD trials between 2002 and 2012, with a failure rate of 99.6 percent (Cummings et al., 2014). Surely the time is now ripe for a clinical trial of an antiviral to combat HSV1 in the disease.


    . Herpes simplex virus type 1 and Alzheimer's disease: increasing evidence for a major role of the virus. Front Aging Neurosci. 2014;6:202. Epub 2014 Aug 11 PubMed.

    . Antivirals reduce the formation of key Alzheimer's disease molecules in cell cultures acutely infected with herpes simplex virus type 1. PLoS One. 2011;6(10):e25152. PubMed.

    . Intravenous immunoglobulin reduces beta amyloid and abnormal tau formation caused by herpes simplex virus type 1. J Neuroimmunol. 2013 Apr 15;257(1-2):7-12. PubMed.

    . The helicase-primase inhibitor BAY 57-1293 reduces the Alzheimer's disease-related molecules induced by herpes simplex virus type 1. Antiviral Res. 2013 Sep;99(3):401-4. PubMed.

    . Alzheimer's disease drug-development pipeline: few candidates, frequent failures. Alzheimers Res Ther. 2014;6(4):37. Epub 2014 Jul 3 PubMed.

    View all comments by Ruth Itzhaki

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