New research has revealed that tau, a protein best known for its connection to Alzheimer’s disease, is also essential for creating lasting memories. The discovery provides new insights into how healthy memory works and could help guide future efforts to develop treatments for dementia.
The study, led by Flinders University in collaboration with researchers from the University of New South Wales and Macquarie University, was published in Nature Communications. He discovered that tau helps organize and stabilize memories so they can be preserved over time.
The researchers studied “remote memory” in mice, which refers to memories recalled days or weeks after an experience. They found that tau is not necessary to learn something new or remember it soon afterward. Rather, it plays a crucial role in making those memories lasting in the long term.
Because the research was conducted in mice, the findings cannot be directly applied to human memory or Alzheimer’s disease. Still, the results offer valuable clues that could shape future dementia research and treatment strategies.
Tau’s role in lasting memory
Lead author Associate Professor Arne Ittner, a neuroscientist at the Flinders School of Medicine and Public Health, says the findings help explain why people with dementia can still learn new information initially, but have difficulty retaining it.
“Why some memories endure while others fade has long baffled scientists and our study shows that tau plays a key role in how the brain forms lasting memories. Without it, memories can still be formed 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 to determine exactly which engram cells are recruited to preserve the experience.
One of the study’s lead authors, Renée Kosonen, says tau acts as an organizer that helps the brain create accurate and long-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 activity or “noise” in the brain during memory formation. By limiting this background activity, tau allows only a specific group of cells to be part of a memory, producing clearer and more stable memory traces.
The team identified an important molecular process behind this effect. As learning occurs, 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. Instead, it appears to be necessary to connect natural cues, such as images and sounds, with the ability to evoke those memories.
The findings also provide new insights 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 these abnormal shapes appeared after memories had already been 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 be due not only to the loss of memories, but also to alterations in the way memories are organized and accessed.
“Knowing how tau supports memory formation and recall could help us better understand what goes wrong in memory loss,” says Associate Professor Ittner.
“Hopefully, future research can confirm the concepts developed in our study on human memory and show their implication in dementia.”
The researchers conclude that tau should be considered not only as a protein implicated in Alzheimer’s disease, but also as a fundamental regulator of how the brain organizes, stores and retrieves long-lasting memories. That new perspective could deepen scientists’ understanding of both healthy memory and the biological changes that contribute to Alzheimer’s disease.