Tau protein tied to long-term memory in mouse study

A protein strongly associated with Alzheimer’s disease also appears to help the brain turn experiences into durable memories, according to a Flinders University-led mouse study. The finding matters because it points to a normal role for tau in memory, while also offering a possible explanation for how abnormal tau may disrupt recall in dementia.

The study, conducted with researchers from the University of New South Wales and Macquarie University, was published in Nature Communications. Flinders University said the work examined “remote memory” in mice, meaning memories recalled days or weeks after an event.

According to the researchers, tau was not required for mice to learn new information or remember it soon afterward. Its role appeared later, when memories needed to be strengthened and maintained over time.

Associate Professor Arne Ittner, a neuroscientist at Flinders’ College of Medicine and Public Health and senior author of the study, said the results may help explain why some people with dementia can take in new information but have trouble keeping it. He said the study indicates tau helps make memories more stable after they first form.

How tau shapes memory traces

The team studied brain cells known as engram cells, which are involved in storing the physical trace of a memory. When an animal has a new experience, a limited set of these cells is recruited to represent it.

Flinders University said the researchers found tau was active during this selection process. Renée Kosonen, one of the study’s lead authors and a researcher at Flinders’ Neuroscience and Dementia Research group, said the protein helps determine which cells are assigned to hold a memory.

The study also found that tau dampens background brain activity during memory formation. By reducing that “noise,” the researchers said, tau helps a more specific group of cells form a clearer and more stable memory trace.

The team identified a molecular change involved in the process: tau phosphorylation. In Alzheimer’s disease, abnormal phosphorylation of tau is a known feature, but the study found that controlled, low-level phosphorylation during learning appears to be part of healthy memory function.

Clues for Alzheimer’s research

The researchers also reported that memory traces could still exist without tau. In mice lacking tau, the team could recover memories by directly stimulating engram cells, suggesting tau is not the storage site for memory itself.

Instead, Flinders University said the protein seems to help link natural cues, such as sights or sounds, to later recall. That distinction could be relevant to dementia research, because memory problems may involve trouble accessing memories as well as trouble forming them.

The study also examined disease-associated forms of tau. When abnormal tau was present in engram cells during learning, it disrupted the formation of new memories, according to the researchers. When it appeared after memories had already formed, it interfered with recall.

Those effects were linked to unusual patterns of brain activity, the researchers said. Ittner said understanding how tau supports both memory formation and retrieval could help clarify what changes during memory loss.

The researchers cautioned that the work was done in mice, so the findings cannot be applied directly to human memory or Alzheimer’s disease. Flinders University said future research will need to test whether the same concepts hold in humans and how they relate to dementia.

The journal paper is titled “Tau T205 phosphorylation modulates engram cell recruitment and remote memory in mice.” Its authors include Kosonen, Kristie Stefanoska, Yijun Lin, Samantha Edwards, Emmanuel Prikas, Josefine Bertz, Anne Poljak, Lars M. Ittner and Arne Ittner.

This story draws on original reporting from ScienceDaily.