Introduction. Over 25 million people in the world are affected by dementia, most suffering from Alzheimer’s Disease (AD), a progressive neurodegenerative disease caused by an accumulation of Aβ amyloid3. However, what triggers this Aβ accumulation has yet to be clearly defined. In this commentary, herpes simplex virus type 1 (HSV-1) will be explored as a possible trigger of Aβ production. Aβ is classified as an antimicrobial peptide produced to protect neurons from infections, since neurons are self-limited and will not be replaced if they undergo apoptosis. 1 Aβ oligomers have been shown to inhibit HSV-1 infection in vitro.1 HSV-1 inhibits the destruction of Aβ oligomers produced by innate immunity, by inhibiting lysosomal and autophagic processes.5 Proving HSV-1 stimulation and dysregulation of Aβ would provide new possible treatment options for AD. Methods. Transgenic mice were given the human Aβ gene and infected with HSV-1. The WT and transgenic mice were compared without HSV-1 present, with HSV-1 present initially, and 21 days post infection with anti-Aβ antibodies, Aβ binding ELISA, immunofluorescence labeling, and TEM analysis of HSV-1, Aβ proteins, and Aβ amyloid plaques. 1 Results. In WT mice, no Aβ was present with or without HSV-1 present, and post infection. In the transgenic mice Aβ was minimally present without HSV-1, highly prevalent in HSV-1 infection, and 21 days post infection HSV-1, Aβ proteins, and Aβ amyloid plaques were all present, and in the same areas. Other studies have shown HSV-1 surface glycoproteins seem to impair endosomal trafficking, including the fusion of lysosomes with autophagosomes,2 as well as, specific HSV-1 proteins phosphorylate eIF2α and interfere with autophagy upregulation.6 Conclusions. These results indicate that HSV-1 does trigger the production of Aβ proteins and Aβ amyloid plaques as part of an immune response to infection and by inhibiting Aβ recycling. This research indicates a possible new target to treat AD by targeting upregulation of autophagy to break down the Aβ oligomers before they form plaques. Lithium is a drug currently on that market that upregulates autophagy4 and can easily cross the blood brain barrier. This commentary explores the potential of lithium as a possible treatment for AD.
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