Independent and Correlated Role of Apolipoprotein E ɛ4 Genotype and Herpes Simplex Virus Type 1 in Alzheimer’s Disease

Article type: Review Article

Authors: Zhang, Li-Na^{a; b; c} | Li, Meng-Jie^{a; b; c} | Shang, Ying-Hui^{a; b; c} | Zhao, Fan-Fan^{a; b; c} | Huang, Han-Chang^{a; b; c} | Lao, Feng-Xue^{a; b; c; *}

Affiliations: [a] Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, Beijing, P.R. China | [b] Institute of Functional Factors and Brain Science, Beijing Union University, Beijing, P.R. China | [c] College of Biochemical Engineering, Beijing Union University, Beijing, P.R. China

Correspondence: [*] Correspondence to: Feng-xue Lao, Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University; Institute of Functional Factors and Brain Science, Beijing Union University; College of Biochemical Engineering, Beijing Union University, Beijing 100191, P.R. China. Tel.: +86 10 62004513; E-mail: [email protected].

Abstract: The ɛ4 allele of the Apolipoprotein E (APOE) gene in individuals infected by Herpes simplex virus type 1 (HSV-1) has been demonstrated to be a risk factor in Alzheimer’s disease (AD). APOE-ɛ4 reduces the levels of neuronal cholesterol, interferes with the transportation of cholesterol, impairs repair of synapses, decreases the clearance of neurotoxic peptide amyloid-β (Aβ), and promotes the deposition of amyloid plaque, and eventually may cause development of AD. HSV-1 enters host cells and can infect the olfactory system, trigeminal ganglia, entorhinal cortex, and hippocampus, and may cause AD-like pathological changes. The lifecycle of HSV-1 goes through a long latent phase. HSV-1 induces neurotropic cytokine expression with pro-inflammatory action and inhibits antiviral cytokine production in AD. It should be noted that interferons display antiviral activity in HSV-1-infected AD patients. Reactivated HSV-1 is associated with infectious burden in cognitive decline and AD. Finally, HSV-1 DNA has been confirmed as present in human brains and is associated with APOE ɛ4 in AD. HSV-1 and APOE ɛ4 increase the risk of AD and relate to abnormal autophagy, higher concentrations of HSV-1 DNA in AD, and formation of Aβ plaques and neurofibrillary tangles.

Keywords: Alzheimer’s disease, apolipoprotein E, cytokine, estrogen therapy, herpes simplex virus type 1, infectious burden, interferon

DOI: 10.3233/JAD-200607

Journal: Journal of Alzheimer's Disease, vol. 77, no. 1, pp. 15-31, 2020