New research has revealed that tau, a protein best known for its connection to Alzheimer’s disease, is also essential for creating long lasting memories. The discovery provides new insight into how healthy memory works and could help guide future efforts to develop treatments for dementia.
The study, led by Flinders University in partnership with researchers from the University of New South Wales and Macquarie University, was published in Nature Communications. It found that tau helps organize and stabilize memories so they can be retained over time.
The researchers studied “remote memory” in mice, which refers to memories recalled days or weeks after an experience. They discovered that tau is not necessary for learning something new or remembering it shortly afterward. Instead, it plays a crucial role in making those memories durable over the long term.
Because the research was conducted in mice, the findings cannot be directly applied to human memory or Alzheimer’s disease. Even so, the results offer valuable clues that could shape future dementia research and treatment strategies.
Tau’s Role in Long Lasting Memory
Senior author Associate Professor Arne Ittner, a neuroscientist from Flinders’ College of Medicine and Public Health, says the findings help explain why people with dementia may still be able to learn new information initially, yet struggle to retain it.
“Why some memories last while others fade has long puzzled scientists and our study shows that tau plays a key role in how the brain forms long-lasting memories. Without it, memories can still form in the moment, but they are weaker,” says Associate Professor Ittner.
The team focused on specialized brain cells called “engram cells,” which create the physical record of a memory. When a new experience occurs, only a small number of these cells are selected to store it.
According to the study, tau is active during this critical stage of memory formation, helping determine exactly which engram cells are recruited to preserve the experience.
One of the study’s lead authors, Renée Kosonen, says tau acts like an organizer that helps the brain build accurate and lasting memories.
“Our findings show that tau helps determine which cells are selected to store a memory, shaping how an experience forms a lasting memory trace,” says Ms Kosonen, a researcher at Flinders’ Neuroscience and Dementia Research.
How Tau Organizes Memory
The researchers also found that tau reduces unnecessary or “noise” activity in the brain during memory formation. By limiting this background activity, tau allows only a specific group of cells to become part of a memory, producing clearer and more stable memory traces.
The team identified an important molecular process behind this effect. As learning takes place, tau undergoes a subtle chemical change called phosphorylation, which helps coordinate the activity of engram cells.
Although abnormal tau phosphorylation is a well known feature of Alzheimer’s disease, the study shows that controlled, low level phosphorylation is a normal and essential part of healthy brain function.
New Clues About Alzheimer’s Disease
The researchers made another surprising discovery. Even in the absence of tau, memory traces still existed and could be recovered by directly stimulating engram cells. This suggests that tau is not required to store memories themselves. Instead, it appears to be needed to connect natural cues, such as sights and sounds, with the ability to recall those memories.
The findings also provide new insight into how Alzheimer’s related tau may interfere with memory. When disease associated forms of tau were present in engram cells during learning, they disrupted the creation of new memories. When those abnormal forms appeared after memories had already formed, they interfered with the brain’s ability to retrieve them.
These effects were associated with abnormal patterns of brain activity, suggesting that memory problems in dementia may result not only from memories being lost, but also from disruptions in how memories are organized and accessed.
“Knowing how tau supports the formation and recall of memory could help us better understand what goes wrong in memory loss,” says Associate Professor Ittner.
“Future research will hopefully be able to confirm concepts developed in our study in human memory and show their implication in dementia.”
The researchers conclude that tau should be viewed not only as a protein involved in Alzheimer’s disease, but also as a fundamental regulator of how the brain organizes, stores, and retrieves lasting memories. That new perspective could deepen scientists’ understanding of both healthy memory and the biological changes that contribute to Alzheimer’s disease.
