Viruses may play a surprising part
A decade of research suggests traumatic brain injury, whether from accidents or high-contact sports, is a standout risk factor for Alzheimerâs and other forms of neurodegenerative decline. Some estimates suggest that up to 10 percent of cases could be attributed to at least one prior head injury, but why is not fully understood. Separately, a growing body of research proposes that viral infection, including a common virus known as herpes simplex one, can also increase susceptibility to these diseases. But all three thingsâhead trauma, viral infection, and dementiaâhave not been directly connected in experimental research, until now.
In lab-grown brain organoids, scientists have been able to model some of the same hallmarks of neurodegenerative disease found in the autopsied brains of humans who suffered these diseases while they were alive. These include accumulations of beta amyloid protein, a metabolic waste product, into structures known as plaques, which disrupt signaling between nerve cells.
For the new lab study, a team of researchers grew a series of brain organoids. Some of the organoids had a dormant form of herpes simplex virusâwhich exists in 80 percent of people by age 60âwhile others were virus-free. Then they jolted all of the brain organoids with two different kinds of tiny metal pistons, a model that has been used by other scientists to mimic head trauma in brain organoids.
âWe think what we found in the 3-D model applies in the living brain,â says Ruth Itzhaki, a visiting professorial fellow at the University of Oxford and co-author on the new study, which was published this month in the journal Science Signaling. âYou get a reactivation of the virus after each blow, and each time damage is done. It all accumulates until, eventually, you get Alzheimerâs.â
In the model organoids that were infected with the virus, after repeated blows to the brain tissue, the dormant viruses woke up and started replicating again. Later, some of the signatures of Alzheimerâs and other dementias began to appear: in particular proliferation of beta-amyloid protein and neuroinflammation. The more blows these tiny organoids took, the more inflammation and beta amyloid the scientists found.
The organoids without any dormant virus only showed a few minor changes after they were hit with the piston, such as an increase over 10 days in the number of glial cells, which act like scar tissue in the brain after an injury. The researchers concluded that repeated blows to the head may contribute to dementia by reactivating latent herpes simplex virus.













