Exploring the Role of Viruses and Immune Responses in Alzheimer Disease: Or Shemesh, PhD

WATCH TIME: 5 minutes

"Initially, these proteins were suspected to be the 'bad guys,' but later, we found that they are actually part of the immune response."

Alzheimer disease (AD) has traditionally been diagnosed based on the presence of β-amyloid plaques and hyperphosphorylated tau (p-tau) in the brain. However, recent research indicates that infections, especially herpes simplex virus 1 (HSV-1), could play a role in the development of this neurological disease. A new study led by Or Shemesh, PhD, an assistant professor at The Hebrew University of Jerusalem School of Pharmacy, investigated the impact of HSV-1 on AD pathology using advanced methods like metagenomics, mass spectrometry, and western blotting to identify HSV-1-related proteins in human brain tissue.

In the study, researchers reported a strong link between ICP27, a protein produced by HSV-1, and the severity of AD. Notably, ICP27 was observed to colocalize with p-tau but not with Aβ, indicating a specific connection between HSV-1 infection and tau pathology. In experiments with human brain organoids infected with HSV-1, investigators noticed an increase in tau phosphorylation. Interestingly, p-tau was observed to inhibit ICP27 expression, reducing neuronal death from 64% to just 7%. This suggests that tau phosphorylation may act as a protective mechanism against viral infection in AD.

Building on these findings, Shemesh discussed the potential role of tau in defending against viral infections in the brain during a recent interview with NeurologyLive^®. In the conversation, Shemesh highlighted the complexity of AD, emphasizing the need to explore how the brain microbiome might influence disease progression. He also addressed the challenges in translating these insights into therapeutic strategies, particularly in light of the multifactorial nature of AD. Given the interaction between viruses, bacteria, and fungi, he underscored how future studies will need to account for these diverse pathogens and their impact on disease development and treatment outcomes.

REFERENCES
1. Hyde VR, Zhou C, Fernandez JR, et al. Anti-herpetic tau preserves neurons via the cGAS-STING-TBK1 pathway in Alzheimer’s disease. Cell Rep. January 2, 2025;10.1016/j.celrep.2024.115109. doi:10.1016/j.celrep.2024.115109