Valacyclovir and Symptomatic Alzheimer Disease

The viral hypothesis of Alzheimer disease (AD) states that neurotropic herpesviruses, especially herpes simplex virus type 1 (HSV-1), may be a cause of, or a contributor to, AD. Although never explicitly stated, the viral hypothesis has 2 temporally disconnected formulations. In one formulation, the viral disease acts in earlier life as an initiator of neurodegeneration that leads decades later to β-amyloidosis, tauopathy, or other neurodegenerative neuropathologies. The second formulation of the viral hypothesis is that neurotropic viruses contribute symptomatically to persons with existing cognitive impairment due to AD or other neurodegenerative disorders. It is well-known that herpesviruses, both HSV-1 and herpes zoster, may remain dormant after an initial infection and then reactivate later in life. A study conducted in Sweden found that 80% of older adults had HSV-1 IgG antibodies, indicating how ubiquitous HSV-1 is in the population. The viral hypothesis implies that reactivated virus could interact with AD pathobiology or could exhibit an independent action that accelerated cognitively relevant neurodegeneration in symptomatic people.