Researchers at the University of Pittsburgh have discovered an unexpected link between Alzheimer’s disease and herpes simplex virus type 1 (HSV-1), suggesting that viral infections may play a role in the condition. The results of the study were published on January 2, 2025 in the journal Cell Reports.
This research also shed light on how the tau protein, often considered harmful in the context of Alzheimer’s, might initially protect the brain against the virus, but end up causing brain damage at a later stage. These findings could pave the way for new treatments targeting both infections and the brain’s immune response.
“Our study challenges the conventional view of tau as solely harmful, by demonstrating that it may initially play a role in the brain’s immune defense,” said lead author Or Shemesh, associate professor in the Department of Ophthalmology. from the University of Pittsburgh. “These results highlight the complexity of the interactions between infections, immune responses and neurodegeneration, offering an innovative perspective and potential new directions for therapeutic development.”
Scientists have identified forms of proteins associated with HSV-1 in brain samples from individuals with Alzheimer’s disease, with higher amounts of the viral proteins co-localized with tangles of phosphorylated tau – one hallmark signs of Alzheimer’s pathology – in areas of the brain that are particularly vulnerable throughout the stages of the disease.
Additional studies in mini-models of cultured human brains suggested that HSV-1 infection may modulate levels of tau protein in the brain and regulate its function, a protective mechanism appearing to decrease post-infection mortality. human neurons.
Although the precise mechanisms by which HSV-1 influences tau and contributes to Alzheimer’s disease still remain unknown, Shemesh and his colleagues plan to explore these questions in their future research. They aim to test therapeutic strategies that could target viral proteins or fine-tune the brain’s immune response, as well as examine whether similar mechanisms are involved in other neurodegenerative diseases, such as Parkinson’s disease and amyotrophic lateral sclerosis.
Other authors of the study are Vanesa Hyde, Chaoming Zhou, Juan Fernandez, Krishnashis Chatterjee, Pururav Ramakrishna, Amanda Lin, Gregory Fisher, Orhan Tunç Çeliker, Jill Caldwell and Leonardo D’Aiuto, all of the University of Pittsburgh; Omer Bender and Daniel Bar, both of Tel Aviv University; and Peter Joseph Sauer and Jose Lugo-Martinez, both of Carnegie Mellon University.
This research was supported by the National Institutes of Health (grant R56-AG069192-01), the National Institute of Neurological Disorders and Stroke (grants 1-R01-NS115082-01A1 and 1-R21-NS096405-01A1), Core Vision Research from the University of Pittsburgh Eye & Ear Institute (grant P30-EY08098) and the Foundation Israeli for Science (grants 654/20 and 632/20).
The interaction between viral infections and neurodegenerative diseases, such as Alzheimer’s disease, opens a promising field of research. This highlights the importance of approaching brain health from a multifactorial perspective, where immune responses and infectious agents are to be considered. By highlighting the potential protective role of tau protein early in infection, we could re-evaluate our treatment strategies in innovative ways. If future studies confirm these results, they could lead to the development of new therapeutic approaches, thus changing the way we perceive and manage these complex diseases.
Good to know: Studies on the link between viruses and neurodegenerative diseases are not limited to Alzheimer’s. Other conditions, such as Parkinson’s disease, could also benefit from this research, paving the way for advancements in the understanding and theory of nervous system diseases. It will therefore be interesting to observe how these discoveries will influence future treatments.
- -
