The emerging mechanism behind viral infections and extracellular vesicles hypotheses leading to neuroinflammation and Alzheimer's disease pathology.

Despite decades of repeated and intense research, the etiology of sudden Alzheimer's disease (AD) symptoms is still unclear. AD progressive pathology mainly involves neuron damage, depositions of amyloid-beta (Aβ), and hyperphosphorylated tau protein. All these defects are manifested by exaggerated cytokine storm and neuroinflammation leading to irreversible brain damage in the long term. Despite the numerous risks and drawbacks associated with AD, it is believed that there is a hidden unknown causative and predisposing factors for AD. Extracellular vesicles (EVs) are small vesicles released by cells as a type of intercellular communication. Several pieces of evidence support the inclusion of viral components within EVs facilitating their penetration into the blood-brain barrier leading to neuroinflammation. In light of the SARS-CoV-19 pandemic and its related neurological complications, it is mandatory to highlight the possibility and viability of viral infections such as varicella-zoster virus (VZV) and herpes simplex virus (HSV) on the onset of AD. Herein, the author is investigating the potential role of VZV and HSV along with highlighting the suggested route of pathogenesis entry resulting in AD manifestations. Additionally, this review aims to summarize the role of EVs in mediating the central nervous system viral infections leading to AD.