The Alzheimer’s protein that also helps build lasting memories — and what scientists just discovered about it

For decades, tau has been cast as one of the villains of dementia. It is the protein that tangles and accumulates in the brains of people with Alzheimer’s disease, and its presence in brain tissue has long been associated with the devastating memory loss that defines the condition.

New Australian research has just turned that picture considerably more complicated – and considerably more interesting.

Scientists from Flinders University, working with colleagues from the University of New South Wales and Macquarie University, have found that tau is not simply a disease-related protein waiting to cause damage. In healthy brains, it plays an essential and previously underappreciated role in building the memories that last.

The research, published in the prestigious journal Nature Communications, shows that tau acts as a kind of organiser during the critical window in which a memory is being formed – helping determine which brain cells are recruited to store an experience, and ensuring that the memory remains strong over time.

Why some memories stick and others don’t

You can probably remember where you were when something significant happened years ago with perfect clarity, while struggling to recall what you had for breakfast on Tuesday. The question of why some memories persist while others fade is one of the longest-standing puzzles in neuroscience.

The new research offers a significant piece of the answer.

The study focused on what scientists call remote memory – memories recalled days or weeks after an experience, rather than moments later. It found that while tau is not required for the initial act of learning or for short-term recall, it is critical for ensuring those memories remain robust over the long term.

At the centre of this process are specialised groups of brain cells called engram cells, which form the physical trace of a memory. When we experience something, only a small subset of these cells is selected to store it. The new research shows that tau is active during this selection process, helping to determine which cells are recruited – and crucially, helping to filter out background noise so that the memory trace is clean and stable rather than fuzzy and diffuse.

“Our findings show that tau helps determine which cells are selected to store a memory, shaping how an experience forms a lasting memory trace,” said Renée Kosonen, one of the study’s lead authors and a researcher at Flinders’ Neuroscience and Dementia Research group.

A surprising molecular mechanism

The researchers also identified precisely how tau performs this function. During the learning process, tau undergoes a subtle chemical modification called phosphorylation – a process by which a phosphate molecule attaches to the protein, subtly changing how it behaves.

This is where the story becomes both surprising and significant. Abnormal tau phosphorylation is one of the defining features of Alzheimer’s disease – the toxic tangles that characterise the condition are formed from tau that has been phosphorylated in a damaging, excessive way. Yet the new research shows that controlled, low-level phosphorylation of tau is not only harmless but essential for normal memory function.

The difference between tau as a helper and tau as a destroyer, in other words, may come down to the precise nature and degree of this chemical modification.

What this means for memory loss in dementia

The researchers also used their findings to shed new light on how abnormal tau disrupts memory in people with Alzheimer’s disease – and the picture that emerges is more nuanced than previously understood.

When disease-associated forms of tau were present in engram cells during the learning process, they interfered with the formation of new memories. When they arrived later, after a memory had already been formed, they disrupted the brain’s ability to access and retrieve memories that were already there.

Strikingly, the research showed that even without functional tau, memory traces still exist in the brain – they simply cannot be accessed through normal cues like sights and sounds. The memory, in a sense, is still there. What is lost is the ability to get to it.

“Knowing how tau supports the formation and recall of memory could help us better understand what goes wrong in memory loss,” said senior author Associate Professor Arne Ittner from Flinders’ College of Medicine and Public Health.

“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.”

An important note on what the research does and doesn’t mean

The study was conducted in mice, and the researchers are careful to note that the findings do not directly translate to human brain function or dementia. Mouse models are a valuable tool in early-stage neuroscience research, but they are not brains, and what holds true in laboratory mice does not always hold true in people.

What the research does offer is a meaningful new framework for understanding tau’s role in the healthy brain – and new directions for scientists developing future treatments for Alzheimer’s disease. If tau can be both a helper and a destroyer depending on how it behaves, there may be ways to preserve its beneficial functions while preventing the toxic accumulation that drives dementia.

That is the work that comes next. For now, the finding that one of the most studied proteins in Alzheimer’s research turns out to be fundamental to how we build lasting memories is, as the researchers put it, an important step in understanding what goes wrong — and potentially what can be done about it.

IMPORTANT LEGAL INFO This article is of a general nature and FYI only, because it doesn’t take into account your personal health requirements or existing medical conditions. That means it’s not personalised health advice and shouldn’t be relied upon as if it is. Before making a health-related decision, you should work out if the info is appropriate for your situation and get professional medical advice.