Alzheimer’s-Linked Gene Behaves as Virus, Scientists Find in Odd Discovery

Two research teams have independently discovered that a cognition-related gene behaves like a virus in the nervous system — passing on its genetic material between neurons.

While scientists are still working to understand the “why” of their discovery, they are in agreement that the mechanism has widespread implications, as it appears necessary for the processes of neuronal plasticity — strengthening connections between nerve cells.

Both teams — from the University of Utah and the University of Massachusetts Medical School — published their findings in the journal Cell.

“This work is a great example of the importance of basic neuroscience research,” Edmund Talley, PhD, said in a press release. Talley is a program director at the National Institute of Neurological Disorders and Stroke (NINDS), which partly funded one of the studies.

“What began as an effort to examine the behavior of a gene involved in memory and implicated in neurological disorders such as Alzheimer’s disease has unexpectedly led to the discovery of an entirely new process, which neurons may use to send genetic information to one another,” Talley said.

Scientists have long known that the gene, called Arc, is crucial for brain function. Flaws in the gene have been linked to Alzheimer’s disease, as well as neurodevelopmental conditions such as autism and schizophrenia.

They also knew that the gene held some similarities to proteins found in certain viruses, including HIV. Such viruses infect cells by building a type of shell, called a viral capsid, which contains its genetic information. Such capsids are released from one cell, then travel to another to insert its genetic information.

To both teams’ surprise, they observed virtually the same thing when they studied the Arc gene. When cells made the Arc protein from the gene, it clumped together into a shape, very much resembling a viral capsid.

A piece of its own genetic code — in the form of an intermediary molecule known as mRNA — was then inserted into the capsid-like structure.

“Beforehand, if I had said to any neuroscientist that this gene sort of acts like a virus, they would have laughed at me,” said Jason Shepherd, PhD, an assistant professor who was senior author of the Utah study, “The Neuronal Gene Arc Encodes a Repurposed Retrotransposon Gag Protein that Mediates Intercellular RNA Transfer.”

“We knew this was going to take us in a completely new direction,” he said.

Both teams then discovered that the capsid-like structure with the genetic material was transferred from one neuron to another, or from a neuron to a muscle.

In the article, “Retrovirus-like Gag Protein Arc1 Binds RNA and Traffics across Synaptic Boutons” — led by UMass Medical School’s Vivian Budnik, PhD, and Travis Thomson, PhD — the other team noted that Arc mRNA was a main component of tiny sacs, called extracellular vesicles, released from neurons.

They noted that the flow of Arc mRNA, contained in the capsid-like structures, went from neurons to muscles at nerve-muscle connections. Both groups also suggested that this transfer was crucial for neuronal plasticity — the process whereby neuronal connections become stronger and more plentiful.

Both teams now plan to further work on understanding why neurons use this virus-like method to transfer Arc mRNA between cells. They also want to examine if the process is involved in the proposed spread of Alzheimer’s toxic proteins throughout the brain.

Such research, they said, may lead to a better understanding of Alzheimer’s and other brain diseases, which, in turn, might boost the development of new treatments.

“This research highlights the fact that we often don’t know where the cool discoveries are going to come from,” Shepherd said. “We need to follow where the science takes us.”