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 article, entitled ‘Anti-herpetic tau preserves neurons via the cGAS-STING-TBK1 pathway in Alzheimer’s disease’ was published 2 January 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 defence,” said senior author Or Shemesh, Assistant Professor in the Department of Ophthalmology at Pitt. “These findings emphasise 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 colocalised 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.
- 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. 2024 Dec 26. doi:10.1016/j.celrep.2024.115109