Tara Spires-Jones

Spires-Jones' research focuses on mechanisms of neurodegeneration in diseases that cause dementia, other neurodegenerative diseases, and ageing.^[15] She focuses specifically on the degeneration of synapses, connections between neurons, in Alzheimer's disease. She made the important discovery that soluble forms of amyloid beta and tau proteins that accumulate in neuropathological lesions in Alzheimer's disease both accumulate within synapses where they contribute to degeneration and cognitive decline. This work started in model systems where she showed that lowering levels of these toxic proteins allows functional recovery. Importantly, her team was the first to discover synaptic localisation of amyloid beta ^[16] and tau ^[17] in synapses in human Alzheimer's brain. This was achieved using a technique she pioneered for use in human autopsy tissue.^[18] She has several collaborations with industry, one of which has contributed to a clinical trial of a drug to remove amyloid beta from synapses in Alzheimer's disease.^[19]

The spread of tau pathology through the brain in Alzheimer's disease correlates strongly with cognitive symptoms, and weherever tau pathology appears in the brain, neuron death occurs. Spires-Jones discovered that in addition to accumulating within synapses, tau spreads trans-synaptically through neural circuits. As a postdoc, she characterized tau pathology and neurodegeneration in the rTg4510 mouse model of tauopathy, the first robust tau mouse model.^[20] As a junior faculty member at Harvard Medical School, Tara published a series of papers with Alix de Calignon who she co-supervised as a PhD student. In these studies, they found that tau aggregation in neurons counterintuitively protects cells from acute death ^[21] and that tau pathology propagates through neural circuits in mice.^[22] In human brain, Tara's group recently observed tau in pre and post-synapses supporting potential tau spread through synapses in human disease.^[17] This paper won the Alzheimer's Association's 2024 Inge Grundke-Iqbal prize recognising the most impactful paper published over the previous two years. These data are important because stopping the spread of tau pathology through the brain has the potential to stop disease progression.

Spires-Jones' research has also shown that alpha-synuclein protein builds up in synapses in Dementia with Lewy Bodies, suggesting that these connections enable the protein to jump between cells, spreading damage through the brain and causing symptoms of dementia.^[23][24]

She has also made important discoveries linking two genetic risk factors for Alzheimer's disease, Apolipoprotein E4 and Clusterin to synaptic degeneration^[25] and has contributed to understanding of synapse degeneration in motorneurone disease, and schizophrenia.^[26]

As well as her academic career, Spires-Jones is also an avid SciFi fan and enjoys spending time with her family (including pets).