Viral infections, neurodegenerative & psychiatric diseases: an arduous search for clues …

Viruses & Alzheimer’s Disease

If a role for infectious diseases in the etiology of Alzheimer’s Disease (AD) was considered for years, the concept faced significant fading with the growing prevalence of the beta amyloid cascade hypothesis (which favored a causative role for the beta amyloid peptide). However, some part of the neuroscience community has expressed some concern about the causative involvement of Abeta, to shift towards a potential -more infection-related - cause of AD. Prof Ruth Itzhaki (University of Manchester, Oxford, UK) suggested in 2014 that «Herpes simplex virus type 1 (HSV1), when present in brain of carriers of the type 4 allele of the apolipoprotein E gene (APOE), has been implicated as a major factor in Alzheimer's disease (AD)» (Itzhaki 2014). HSV1 is a virus that is able to establish of latent infections in sensory neurons that accounts for the widespread dissemination of life long infections in humans. Periodic reactivation of latent virus results in asymptomatic shedding and transmission of HSV1 or recurrent disease that is usually mild (herpes labialis). However, acute HSV1 infection can be severe, leading to the potentially lethal Herpes Simplex Encephalitis. Strikingly, a study published in 2018 reported a decrease in the relative risk of Senile Dementia by a factor of 10 in a longitudinal 10 years follow-up of patients treated aggressively with antiherpetic medications, while the hazard ratio for the development of dementia in the HSV infected-cohort was 2.5 higher than the non-infected cohort (Tzeng, Chung et al. 2018). Another study in 2018 suggested that the fibrilization pathways of Abeta mediate antiherpetic activity, thus conferring protection against infectious agents (in this study against the neurotropic herpes simplex virus 1 (HSV1) and human herpesvirus 6 (HHV6)) (Eimer, Vijaya Kumar et al. 2018). A randomised, double-blind, placebo-controlled, treatment trial with the antiviral Valacyclovir, initiated in 2020, is currently ongoing and assessed on cognitive decline (Devanand, Andrews et al. 2020) of AD patients.

Could AD be a “mild” chronic form of HSV1 infection developing in some patients who have escaped the acute infectious form (Herpes Simplex Encephalitis) that engenders strong memory disorders? This question obviously should draw attention on the potential danger of infections considered harmless so far, as is herpes labialis. Moreover, neuroinflammation has been shown to play a key role in AD: thus, many viruses other than HSV1 might induce memory problems if they are able to enter the brain and establish a dormat state associated to low level inflammation. Indeed, memory problems have also been reported in Covid patients (Fotuhi, Mian et al. 2020).

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Viruses & Multiple Sclerosis

Data accumulate which highlight an important role of both autoimmune inflammation and progressive neurodegeneration in the pathophysiology of multiple sclerosis (MS). Despite an obvious success in reducing the burden of ... read more