New research reveals that tau, the protein best known for its association with Alzheimer’s disease, is also essential for the formation of long-term memories. The findings provide new insights into how healthy memory works and could guide future efforts to develop treatments for dementia.
The study was led by Flinders University in collaboration with researchers from the University of New South Wales and Macquarie University. nature communications. It turns out that tau helps organize and stabilize memories, allowing them to be retained over time.
Researchers used mice to study “remote memory.” This refers to memories recalled days or weeks after an experience. They discovered that you don’t need tau to learn something new and remember it quickly afterwards. Rather, it plays an important role in the long-term persistence of memory.
Because this study was conducted in mice, the results cannot be directly applied to human memory or Alzheimer’s disease. Still, the results provide valuable clues that may shape future dementia research and treatment strategies.
The role of tau in long-term memory
Lead author Associate Professor Arne Ittner, a neuroscientist at Flinders School of Medicine and Public Health, said the findings help explain why people with dementia are initially able to learn new information, but then struggle to retain it.
“Scientists have long puzzled why some memories persist while others fade, but this study shows that tau plays an important role in how the brain forms long-term memories. Without tau, memories are formed in the moment, but they are weaker,” Ittner said.
The research team focused on specialized brain cells called “engram cells,” which create physical records of memories. When a new experience occurs, only a small number of these cells are selected to store it.
Research shows that tau is active during this critical stage of memory formation, helping to determine precisely which engram cells are recruited to store experiences.
Renee Kosonen, one of the study’s lead authors, said 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 memories, and how experiences form lasting memory traces,” says Ms Kosonen, a researcher in neuroscience and dementia research at Flinders.
How Tau organizes memories
Researchers also found that tau reduces unnecessary or “noise” activity in the brain during memory formation. By limiting this background activity, tau allows only certain groups of cells to become part of the memory, producing a more vivid and stable memory trace.
The research team identified a key molecular process behind this effect. When learning occurs, tau undergoes a subtle chemical change called phosphorylation, which helps regulate engram cell activity.
Although abnormal tau phosphorylation is a well-known feature of Alzheimer’s disease, this study shows that regulated, low-level phosphorylation is an important part of normal, healthy brain function.
New clues about Alzheimer’s disease
Researchers made another surprising discovery. Even in the absence of tau, memory traces were still present and could be recovered by directly stimulating engram cells. This suggests that tau itself is not required to store memory. 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 tau, which is associated with Alzheimer’s disease, interferes with memory. When disease-associated forms of tau were present in engram cells during learning, they prevented the generation of new memories. When those abnormal forms appeared after the memory had already been formed, they interfered with the brain’s ability to retrieve the memory.
These effects are associated with abnormal patterns of brain activity, suggesting that memory impairment in dementia may be caused not only by memory loss but also by disruptions in how memories are organized and accessed.
“Knowing how tau supports memory formation and retrieval may help us better understand what’s wrong with memory loss,” Ittner says.
“We hope that future studies will confirm the concepts developed in our study in human memory and show implications for 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. This new perspective could improve scientists’ understanding of both healthy memory and the biological changes that contribute to Alzheimer’s disease.
