Brain's Memory Mechanism Revealed: Controlled Amyloid Formation Turns Experience Into Lasting Recall

For more than a century, neuroscientists have puzzled over a simple question: why do some moments stick with us while others dissolve? A team at the Stowers Institute believes they have finally found the answer, and it upends everything we thought we knew about one of the brain's most notorious villains.

Amyloids have long been the enemy in neuroscience. These are misfolded proteins that clump together into tight, stable fibers, and they are the hallmark of Alzheimer's, Huntington's, and Parkinson's disease. They accumulate in the brain, destroy neurons, and erase memories. For decades, scientists treated amyloid formation as a malfunction—an unintended consequence of aging and disease. But a study published this month in the Proceedings of the National Academy of Sciences suggests amyloids are not always destructive. Sometimes, the brain deliberately makes them. And when it does, they become the physical basis of memory itself.

Kausik Si, the Scientific Director at Stowers, has spent more than twenty years chasing this idea. In 2003, he discovered the first evidence of a functional amyloid in the sea slug, an organism with only ten thousand neurons. From there, his lab expanded the work to fruit flies, mice, and humans, finding that the same mechanism appeared across species of vastly different complexity. But knowing that amyloids could support memory was not the same as understanding how the brain controlled the process. "Despite one hundred years of studying amyloid biology, nobody has ever asked how the brain can deploy amyloid," Si said. "Because amyloid formation was historically thought to be unintentional and unintended, it was necessary for us to ask that question."

The breakthrough came through a protein called Orb2 in fruit flies, which must assemble into an amyloid at the synapses—the gaps between neurons—for a memory to persist. The researchers hypothesized that the difference between a harmful amyloid and a helpful one might depend on whether this assembly process was tightly controlled by other proteins. To test this, they screened thirty different chaperon proteins, which are molecules that guide other proteins into their proper shapes. What they found was a previously unknown chaperon that did something unexpected: instead of preventing amyloid formation, it actively enabled it. They named it Funes, after a Jorge Luis Borges character cursed with perfect memory.

The evidence was striking. Researchers trained hungry fruit flies to associate a specific smell with a sugar reward, then tested their memory after twenty-four hours. Flies with elevated levels of Funes remembered the link far better than normal flies. But the most telling experiment came when Rubén Hervas, now a professor at the University of Hong Kong, engineered Funes variants that could bind to Orb2 but could not trigger its transformation into amyloid. Those flies lost their long-term memory entirely. Funes was not just helpful; it was essential.

The implications ripple outward in unexpected directions. While screening the chaperon proteins, the team noticed something curious: the human versions of these genes have been implicated in schizophrenia, according to genome-wide association studies. Patton, the lead author on the study, was careful not to overstate the connection. Schizophrenia is not simply a disease of broken chaperons. But the overlap suggests these proteins may play a role in how the brain perceives and processes the world. "In diseases where we do not see the world as it is, like schizophrenia or bipolar disorder, we could imagine chaperons playing a role," Si said.

The practical applications could be profound. If scientists can understand how Funes controls amyloid formation, they might be able to activate these chaperons to guide toxic amyloids toward being less harmful, or to enhance the brain's capacity to form functional amyloids that could override disease-causing ones. It is a reversal of decades of amyloid research, which focused almost entirely on stopping amyloid formation. Now the question becomes: how do we make the right kind of amyloid, in the right place, at the right time? The answer, it turns out, began with a sea slug.