HMN 2026: How Alzheimer’s-linked protein is found to shape long-term memories

New research has uncovered how a protein strongly linked to Alzheimer’s disease plays a critical role in forming long-lasting memories—opening up new directions for future dementia treatments.

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 and shows that tau—a protein widely associated with memory loss in dementia—is essential for organizing and stabilizing memories so they persist over time. The paper is titled “Tau T205 phosphorylation modulates engram cell recruitment and remote memory in mice.”

The research focused on “remote memory” in mice—memories recalled days or weeks after an experience—and found that while tau is not required for initial learning or short-term recall, it is critical for ensuring memories remain strong over the long term.

While these findings were observed in mice and do not directly translate to human brain function or dementia, they offer important insights that could help guide the development of future treatments.

Explaining dementia-related memory loss

Senior author and neuroscientist, Associate Professor Arne Ittner, says the work helps explain why memory loss in dementia can develop even when initial learning appears intact.

“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, from Flinders’ College of Medicine and Public Health.

At the heart of this process are specialized groups of brain cells known as “engram cells,” which form the physical trace of a memory. During learning, only a small subset of these cells is recruited to store a given experience.

The study shows that tau acts during this critical encoding window, helping determine which cells are selected to store a memory.

One of the lead authors, Renée Kosonen, says tau functions as a kind of organizer, ensuring memory formation is precise.

“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.

Importantly, the researchers found that tau helps prevent excess or “noise” activity in the brain, allowing only a specific group of cells to become part of the memory trace, resulting in clearer, more stable memories.

The role of phosphorylation in memory

The researchers also identified a key molecular mechanism behind this effect. During learning, tau undergoes a subtle chemical modification known as phosphorylation, which helps coordinate the activity of engram cells.

While abnormal tau phosphorylation is a hallmark of Alzheimer’s disease, this study shows that controlled, low-level phosphorylation plays an essential role in normal brain function.

What happens when tau goes wrong

Interestingly, the researchers found that memory traces still exist even without tau—and could be accessed by directly stimulating engram cells. This suggests tau is specifically required to link natural cues, such as sights or sounds, to memory recall, rather than to store the memory itself.

The study also sheds light on how abnormal tau disrupts memory in dementia. When disease-associated forms of tau were present in engram cells during learning, they interfered with the formation of new memories. When present later, they disrupt the brain’s ability to access existing memories.

These disruptions were linked to abnormal brain activity, suggesting that memory problems in dementia may arise not only from lost memories, but also from impaired organization and retrieval.

Implications for future dementia treatments

“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 implications in dementia.”

The researchers say the findings position tau not just as a disease-related protein, but also as a fundamental regulator of how memories are organized and retained—providing new insight into both healthy brain function and the mechanisms underlying memory loss in Alzheimer’s disease.

The content is provided for information purposes only.