University of Pittsburgh researchers uncovered a surprising link between Alzheimer’s disease and herpes simplex virus-1 (HSV-1), suggesting that viral infections may play a role in the disease. The study results were published Jan. 2, 2025, in Cell Reports.
The study also revealed how tau protein, often viewed as harmful in Alzheimer’s, might initially protect the brain from the virus but contribute to brain damage later. These findings could lead to new treatments targeting infections and the brain’s immune response.
“Our study challenges the conventional view of tau as solely harmful, showing that it may initially act as part of the brain’s immune defense,” said senior author Or Shemesh, above, assistant professor in the Department of Ophthalmology at Pitt. “These findings emphasize the complex interplay between infections, immune responses and neurodegeneration, offering a fresh perspective and potential new targets for therapeutic development.”
The scientists identified forms of HSV-1-related proteins in Alzheimer’s brain samples, with greater amounts of viral proteins colocalized with tangles of phosphorylated tau—one of the hallmarks of Alzheimer’s pathology—in brain regions especially vulnerable to Alzheimer’s across disease stages.
Further studies on miniature models of human brains in a Petri dish suggested that HSV-1 infection could modulate levels of brain tau protein and regulate its function, a protective mechanism that seemed to decrease post-infection death of human neurons.
While the precise mechanisms by which HSV-1 influences tau protein and contributes to Alzheimer’s disease are still unknown, Shemesh and his colleagues plan to explore those questions in future research. They aim to test potential therapeutic strategies that target viral proteins or fine-tune the brain’s immune response and investigate 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 Pitt; 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), National Institute of Neurological Disorders and Stroke (grants 1-R01-NS115082-01A1 and 1-R21-NS096405-01A1), University of Pittsburgh Eye & Ear Institute Core Vision Research (grant P30-EY08098) and the Israeli Science Foundation (grants 654/20 and 632/20).