While Itzhaki’s work has been widely recognized, it has met considerable resistance in the United States. A statement at the top of his piece may explain why. “Infected” is not the same as “affected.” Yes, not all of those who have HSV1 will develop AD. Other factors influence the risk. Similarly, another virus in the herpes family, varicella, infects most people and causes chicken pox; yet, only a small portion experience a viral reactivation and develop shingles decades later.

Itzhaki’s group has tested the viability of a vaccine against HSV1. Mice treated with an experimental vaccine can be exposed to HSV1 without the virus establishing persistent latent infections, unlike unvaccinated mice.16 Until a human vaccine can be developed, there are interventions currently available. Antiviral medications, such as acyclovir and valacyclovir, are highly effective against HSV1. As mentioned above, acyclovir prevented the accumulation of amyloid in virally infected neurons in culture. However, acyclovir has poor oral bioavailability and is rapidly eliminated (half-life of 3 hours).


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The pro-drug, valacyclovir has 3-5 times greater bioavailability.17,18 Moreover, valacyclovir is safe and well-tolerated unless there is renal impairment. In my experience, valacyclovir can be administered for years to treat virally-mediated illnesses without any detectable adverse events.19 Similarly, a group of patients with multiple sclerosis were treated for two years with valacyclovir with no adverse consequences.20

In summary, if findings by the Swedish group4 and Itzhaki are correct, and a shift in intrinsic assumptions about Alzheimer’s can occur, then antiviral treatments currently available could potentially eliminate a significant proportion of Alzheimer’s cases.21 The low cost and risk of obtaining blood work on Alzheimer’s patients and administering valacyclovir comes with a potentially huge upside. The alternative is to wait for the autopsy.

Theodore Henderson, MD, PhD, is a psychiatrist in Denver who specializes in the diagnosis of complex adult, child, and adolescent psychiatric cases. His website is www.childpsychiatristdenver.com.

References

  1. Henderson TA. The diagnosis and evaluation of dementia and mild cognitive impairment with emphasis on SPECT perfusion neuroimaging. CNS Spectr. 2012; 17(4):176-206.
  2. Hebert LE, et al. Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch Neurol. 2003; 60(8) 1119–1122.
  3. Alzheimer’s Association. 2014 Alzheimer’s Disease Facts and Figures http://www.alz.org/downloads/Facts_Figures_2014.pdf . Accessed October 29, 2014.
  4. Lövheim H, et al. Herpes simplex infection and the risk of Alzheimer’s disease — A nested case-control study. Alzheimers Dement. 2014; doi: 10.1016/j.jalz.2014.07.157.
  5. Reinberg S. Studies Link Cold Sore Virus to Alzheimer’s Risk. HealthDay. Published Oct. 24, 2014.
  6. Smith JS and Robinson NJ. Age-specific prevalence of infection with herpes simplex virus types 2 and 1: a global review. J. Infect. Dis. 2002; 186 Suppl 1: S3–28.
  7. Jamieson GA, et al. Latent herpes simplex virus type 1 in normal and Alzheimer’s disease brains. J Med Virol. 1991; 33(4):224-7.
  8. Jamieson GA, et al. Herpes simplex virus type 1 DNA is present in specific regions of brain from aged people with and without senile dementia of the Alzheimer type. J Pathol. 1992; 167(4):365-8.
  9. Jamieson GA, et al. Herpes simplex virus type 1 DNA sequences are present in aged normal and Alzheimer’s disease brain but absent in lymphocytes. Arch Gerontol Geriatr. 1992; 15 Suppl 1:197-201.
  10. Itzhaki RF, et al. The role of viruses and of APOE in dementia. Ann N Y Acad Sci. 2004; 1019:15-8.
  11. Wozniak MA, et al;. Herpes simplex virus infection causes cellular beta-amyloid accumulation and secretase upregulation. Neurosci Lett. 2007; 429(2-3):95-100.
  12. Shipley SJ, et al. Herpes simplex virus interferes with amyloid precursor protein processing. BMC Microbiol. 2005; 5:48.
  13. Wozniak MA, et al. Alzheimer’s disease-specific tau phosphorylation is induced by herpes simplex virus type 1. J Alzheimers Dis. 2009; 16(2):341-50.
  14. Wozniak MA, et al. 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.
  15. Wozniak MA, et al. Herpes simplex virus type 1 DNA is located within Alzheimer’s disease amyloid plaques. J Pathol. 2009; 217(1):131-8.
  16. Lin WR, et al. Vaccination prevents latent HSV1 infection of mouse brain. Neurobiol Aging. 2001; 22(5): 699-703.
  17. Weller S, et al. Pharmacokinetics of the acyclovir pro-drug valaciclovir after escalating single- and multiple-dose administration to normal volunteers. Clin Pharmacol Ther. 1993; 54(6):595-605.
  18. Soul-Lawton J, et al. Absolute bioavailability and metabolic disposition of valaciclovir, the L-valyl ester of acyclovir, following oral administration to humans. Antimicrob Agents Chemother. 1995;  39(12):2759-2764.
  19. Henderson TA. Valacyclovir treatment of chronic fatigue in adolescents. Adv Mind Body Med. 2014; (1):4-14.
  20. Friedman JE, et al. A randomized clinical trial of valacyclovir in multiple sclerosis. Mult Scler. 2005;11(3):286-95.
  21. Wozniak MA and Itzhaki RF. Antiviral agents in Alzheimer’s disease: hope for the future? Ther Adv Neurol Disord. 2010; 3(3):141-52.