Herpes Simplex Virus and Neurodegeneration: Evidence

Herpes Simplex Virus Type 1 (HSV)

Affects the CNS

Causes sores

Contagious

Skin-to-skin contact transmission

No cure

Infects epithelial cells of oral and nasal mucosa

Replicates

Enters sensory neurons and establishes a latent infection

HSV and Alzheimer's Disease (AD)

HSV DNA found in many brains of elderly people in its latent forms

Located within amyloid plaques in AD brains

Reactivates in brain causing infection which leads to severe damage and cell death

HSV hijacks cell machinery and binds to proteins that regulate apoptosis

Could reactivation cause gradual, localized damage which could lead to development of AD?

Apoptosis is important in degradation of amyloid proteins

Lack of apoptosis leads to accumulation of beta amyloid and tau

Epidemiological

HSE affects the same brains involved in AD in humans and rodents

Other infectious agents can reactivate and replicate in the CNS

Genetic

Immunological

Genes that mediate viral entry into neurons and defense mechanism could be working mechanistically to cause AD

HSV infection could increase risk of AD in APOE-E4 carriers

Anti-HSV IgM associated with reactivation of HSV

Anti-HSV IgG demonstrates only in persons infected with HSV

Letenneur et al. (2008): IgM-positive more likely to develop dementia

High IgM levels --> low plasma levels of AB1-40 and AB1-42--> high amyloid beta in brain cells

virus reactivation --> changes in APP process --> AD

Molecular evidence

HSV affects APP processing

HSV contributes to production of APP cleavages/fragments which have neurotoxic effects that lead to AD

HSV can bind to neuronal membranes which leads to neuronal degeneration

HSV can cause Ca-mediated APP phosphorylation