Synaptic propagation of tau in Alzheimer’s disease and Progressive Supranuclear Palsy
In Alzheimer’s disease (AD) and Progressive Supranuclear Palsy (PSP), tau pathology spreads through the brain in a stereotypical pattern, and where tau pathology appears in the brain, synapse and neuron loss follows. In cell and animal models of tauopathy, pathological tau spreads via synapses and glia have been shown to play a role in tau propagation, the synaptic spread of pathological tau, and tau-induced neurodegeneration. Here we will present data investigating trans-synaptic tau spread in human brain and living human organotypic brain slices. Immunohistochemistry, array tomography, and confocal imaging were used to study post-mortem brain samples from people with Alzheimer’s disease, Progressive Supranuclear Palsy, control subjects, and human organotypic brain slices challenged with proteins extracted from PSP brain samples. Data were analyzed with linear mixed effects models to examine the effects of disease and sex with case used as a random effect to avoid pseudoreplication. We observe that in both AD and PSP, oligomeric tau is found in synaptic pairs even in brain regions that are affected late in the disease process. Further, there is an increased ingestion of synapses by astrocytes in these tauopathies. Exposing living human organotypic brain slices to pathological tau derived from PSP brain tissue causes post-synaptic uptake of oligomeric tau and astrogliosis. Together, these data from human brain support the idea that tau pathology spreads through the brain trans-synaptically and that astrocytes play a role in synapse degeneration. In the future, therapies aimed at preventing synaptic spread of tau may be beneficial in AD and PSP.

SPEAKER BIOGRAPHY

Professor Tara Spires-Jones, DPhil(Oxon), FMedSci is the Personal Chair of Neurodegeneration and Director of the Centre for Discovery Brain Sciences at the University of Edinburgh. Her research focuses on the mechanisms and reversibility of neurodegeneration in Alzheimer’s disease, other degenerative brain diseases, and ageing. Working with a vibrant group of researchers, she is trying to understand why synapses and neurons become dysfunctional and degenerate. Her work has shown that soluble forms of the pathological proteins amyloid beta and tau contribute to synapse and neuron degeneration. Further, her group has discovered that pathological forms of tau spread through the brain via synaptic connections. Tara Spires-Jones has published over 150 peer-reviewed papers which have been cited over 25,000 times.

Prof Spires-Jones trained in Biochemistry and French at the University of Texas at Austin as an undergraduate and earned a masters and DPhil from the University of Oxford supervised by Prof Sir Colin Blakemore. She then moved to Massachusetts General Hospital and Harvard Medical School for postdoctoral training with Prof Bradley Hyman where she stayed and started a group as Instructor then and Assistant Professor. In 2013 she moved to the University of Edinburgh as Reader and Chancellor’s Fellow and has won prestigious funding including a European Research Council Consolidator Award and a position as a UK Dementia Research Institute Group Leader.

In addition to her research, Prof Spires-Jones is passionate about communicating scientific findings to the public and policy makers; increasing the rigour and reproducibility in translational neuroscience; promoting inclusivity and diversity in science; and supporting career development of neuroscientists. She is President of the British Neuroscience Association (2023-2025), and is founding editor of the translational neuroscience journal Brain Communications. She was also a founding member of the FENS-Kavli Network of Excellence, which works to promote the future of European Neuroscience. In 2024, Prof Spires-Jones was elected a fellow of the UK Academy of Medical Sciences.
Date: 31 January 2025, 13:00
Venue: Sherrington Library, off Parks Road OX1 3PT
Venue Details: Sherrington Building
Speaker: Professor Tara Spires-Jones (University of Edinburgh)
Organising department: Department of Physiology, Anatomy and Genetics (DPAG)
Organisers: Dr Mootaz Salman (DPAG, University of Oxford), Associate Professor Samira Lakhal-Littleton (DPAG, University of Oxford)
Organiser contact email address: events@dpag.ox.ac.uk
Host: Dr Mootaz Salman (DPAG, University of Oxford)
Part of: DPAG Head of Department Seminar Series
Booking required?: Not required
Audience: Members of the University only
Editor: Hannah Simm