Alzheimer's tau protein has a surprising secret role in memory
New research reveals 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 guide future dementia treatments.
A new study led by Flinders University in partnership with the University of New South Wales and Macquarie University, published in Nature Communications, has found that the tau protein, previously primarily linked to Alzheimer's disease, is crucial for forming long-term memories.
The researchers studied "remote memory" in mice—memories recalled days or weeks after an experience. They discovered that tau is not necessary for learning new things or remembering them shortly afterward, but it plays a critical role in making those memories durable over time. Because the study was conducted in mice, the findings cannot be directly applied to human memory or Alzheimer's, but they offer valuable clues for future dementia research.
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 initially learn new information but struggle to retain it. He notes that tau plays a key role in how the brain forms long-lasting memories—without it, memories can form but are weaker.
The team focused on specialized brain cells called "engram cells," which create the physical record of a memory. According to the study, tau is active during this critical memory formation stage, helping determine which engram cells are selected to preserve the experience.
One of the lead authors, Renée Kosonen, a researcher at Flinders' Neuroscience and Dementia Research, says tau acts as an organizer, helping the brain build accurate and lasting memories. The study also found that tau reduces unnecessary or "noise" activity in the brain during memory formation, allowing only a specific group of cells to become part of a memory, producing clearer and more stable memory traces.
New clues about Alzheimer's disease
The team identified an important molecular process: during learning, tau undergoes a subtle chemical change called phosphorylation, which helps coordinate engram cell activity. 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.
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 but appears necessary to connect natural cues, such as sights and sounds, with the ability to recall those memories.
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.
Associate Professor Ittner concludes 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 deepen scientists' understanding of both healthy memory and the biological changes contributing to Alzheimer's disease.
