Skip to main content
Navigate back to homepage
Open search bar.
Open main navigation menu

Main navigation

  • Study
    UCL Portico statue
    Study at UCL

    Being a student at UCL is about so much more than just acquiring knowledge. Studying here gives you the opportunity to realise your potential as an individual, and the skills and tools to thrive.

    • Undergraduate courses
    • Graduate courses
    • Short courses
    • Study abroad
    • Centre for Languages & International Education
  • Research
    Tree-of-Life-MehmetDavrandi-UCL-EastmanDentalInstitute-042_2017-18-800x500-withborder (1)
    Research at UCL

    Find out more about what makes UCL research world-leading, how to access UCL expertise, and teams in the Office of the Vice-Provost (Research, Innovation and Global Engagement).

    • Engage with us
    • Explore our Research
    • Initiatives and networks
    • Research news
  • Engage
    UCL Print room
    Engage with UCL

    Discover the many ways you can connect with UCL, and how we work with industry, government and not-for-profit organisations to tackle tough challenges.

    • Alumni
    • Business partnerships and collaboration
    • Global engagement
    • News and Media relations
    • Public Policy
    • Schools and priority groups
    • Visit us
  • About
    UCL welcome quad
    About UCL

    Founded in 1826 in the heart of London, UCL is London's leading multidisciplinary university, with more than 16,000 staff and 50,000 students from 150 different countries.

    • Who we are
    • Faculties
    • Governance
    • President and Provost
    • Strategy
  • Active parent page: Brain Sciences
    • Study
    • Research
    • About the Faculty
    • Institutes and Divisions
    • Active parent page: News and Events
    • Contact

Brain damage starts before tau protein clumps in frontotemporal dementia and Alzheimer’s

New study led by Prof Karen Duff, Dr Naoto Watamura, & Dr Martha Foiani (UK DRI at UCL) with Prof Takaomi Saido (Riken Center for Brain Science, Japan) reveals insight into the early stages of toxic tau protein build-up in diseases like frontotemporal dementia (FTD)& Alzheimer's.

9 January 2025

Breadcrumb trail

  • Brain Sciences
  • News and Events

Faculty menu

  • Current page: Faculty news
  • Events

The research, published in Nature Neuroscience, could help develop new therapies targeting the earliest stages of these conditions. 

What was the challenge? 

The accumulation of tau protein is a key feature of several neurodegenerative conditions, including FTD and Alzheimer’s. However, what causes this build-up, and which form of tau is most harmful to brain cells is not well understood. One challenge is the lack of good research models to better understand how these diseases start and progress. In this study, the team set out to investigate the earliest stages of disease, using a new mouse model.

What did the team do and what did they find? 

The researchers developed a mouse model expressing human-like versions of tau, but with genetic mutations linked to FTD. They found that the mice had abnormal tau in the hippocampus and entorhinal cortex, brain regions involved in memory and navigation. However, they did not develop the larger clumps of tau, known as fibrils, that are often seen in more advanced stages of disease. 

Even without fibrils, the researchers found that the accumulation of abnormal tau was linked to damaged neurons, loss of synapses – the connections between brain cells – and signs of abnormal behaviour in the mice. This suggests that damage to cells can occur before tau starts to form fibrils, which were previously thought to be an essential step in how tau instigated damage to the brain.

What is the impact? 

This research highlights the significance of targeting the right form of tau and indicates that smaller forms of tau may contribute more to disease symptoms than the larger fibril structures. The study unlocks key insights into the earliest stages of disease, and could aid in the development of new therapies. 

Prof Duff explained:  “By using new models that closely mimic what occurs in human disease, we have shown that brain damage, synapse loss, and cognitive decline can happen even before tau forms into larger clumps. This underscores the need for earlier diagnosis, so that disease can be detected before the damage starts to occur. Our new models will aid in our understanding of the underlying causes of neurodegeneration, and in the development of new therapeutics.” 

Links

  • Watamura, N., Foiani, M.S., Bez, S. et al. In vivo hyperphosphorylation of tau is associated with synaptic loss and behavioral abnormalities in the absence of tau seeds. Nat Neurosci (2024). https://doi.org/10.1038/s41593-024-01829-7
  • Professor Karen Duff's profile

Source

  • UK DRI 
 

UCL footer

Visit

  • Bloomsbury Theatre and Studio
  • Library, Museums and Collections
  • UCL Maps
  • UCL Shop
  • Contact UCL

Students

  • Accommodation
  • Current Students
  • Moodle
  • Students' Union

Staff

  • Inside UCL
  • Staff Intranet
  • Work at UCL
  • Human Resources

UCL social media menu

  • Link to Soundcloud
  • Link to Flickr
  • Link to TikTok
  • Link to Youtube
  • Link to Instagram
  • Link to Facebook
  • Link to Twitter

University College London, Gower Street, London, WC1E 6BT

Tel: +44 (0) 20 7679 2000

© 2025 UCL

Essential

  • Disclaimer
  • Freedom of Information
  • Accessibility
  • Cookies
  • Privacy
  • Slavery statement
  • Log in