Tara Spires-Jones Explained

Tara Spires-Jones
Birth Name:Tara Spires
Fields:Neuroscience
Workplaces:Massachusetts General HospitalHarvard Medical SchoolUniversity of Edinburgh
Alma Mater:University of Texas at AustinUniversity of Oxford
Thesis Title:Genetic and epigenetic interactions in activity-dependent cortical plasticity.
Thesis Year:2003
Known For:Researching mechanisms of synapse degeneration in Alzheimer’s disease.

Tara Spires-Jones is professor of neurodegeneration and deputy director of the Centre for Discovery Brain Sciences at the University of Edinburgh.[1]

Education and career

Spires-Jones studied as an undergraduate at the University of Texas at Austin, where she graduated as a Bachelor of Science in biochemistry and a Bachelor of Arts in French in 1999. She was awarded a British Marshall Scholarship, which enabled her to undertake a D.Phil. in environmental influences on synapse development and degeneration with Prof Sir Colin Blakemore at the University of Oxford.[2] After completing her D.Phil. in 2004, Spires-Jones worked with Dr Bradley T Hyman as a postdoctoral research fellow in neurology at Massachusetts General Hospital and Harvard Medical School, where she undertook research on synaptic degeneration and Alzheimer's disease pathogenesis.[3] Following her fellowship she remained at Massachusetts General Hospital and Harvard Medical School as an instructor from 2006 to 2011 and assistant professor from 2011 to 2013. In 2013 Spires-Jones moved to Scotland to join the University of Edinburgh as reader and Chancellor's Fellow. She was awarded the Personal chair of Neurodegeneration at the university in 2017.

Spires-Jones is a Federation of European Neuroscience Societies (FENS)-KAVLI Network of Excellence scholar, a Scientific Advisory Board Member for Alzheimer's Research UK and the former chair of their Grant Review Board [4] and served as a member of the Scottish Government's Scottish Science Advisory Council.[5] Spires-Jones is founding editor of the translational neuroscience journal Brain Communications.[6]

She is an active member of the British Neuroscience Association, the UKs national society for neuroscientists, serving as president elect from 2021-2023, president 2023-2025, and immediate past president 2025-2027.[7]

Spires-Jones regularly engages in science communication, outreach and engagement,[8] [9] [10] [11] [12] [13] and is a member of the Science Media Centre, advising journalists on science reporting, and commenting on new science stories.[14]

Research

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 synapse connections between neuronal braincells 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 very recently observed tau in pre and post-synapses supporting potential tau spread through synapses in human disease.[17] 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]

Notes and References

  1. News: Prof Tara Spires-Jones. The University of Edinburgh. 2018-10-09. en.
  2. News: Tara SPIRES-JONES. Office. FENS. FENS.org. 2018-10-09. en.
  3. Web site: Professor Tara Spires-Jones The Scottish Science Advisory Council. www.scottishscience.org.uk. en. 2018-10-09.
  4. Web site: Scientist Focus: Dr Tara Spires-Jones Alzheimer's Research UK Blog. www.dementiablog.org. en-US. 2018-10-10.
  5. Web site: Professor Tara Spires-Jones The Scottish Science Advisory Council. www.scottishscience.org.uk. en. 2018-10-10.
  6. Web site: Brain Communications. en-gb . 2023-10-04.
  7. Web site: ANNOUNCING OUR NEW BNA PRESIDENT-ELECT: TARA SPIRES-JONES. 2021-04-15. British Neuroscience Association. en-gb . 2023-10-04.
  8. News: NCTalks with Tara Spires-Jones: ApoE4, synapse degeneration and Alzheimer's - Neuro Central. 2018-04-09. Neuro Central. 2018-10-12. en-US.
  9. Web site: Long Interview: Tara Spires-Jones, 14/07/2018, Good Morning Scotland - BBC Radio Scotland. BBC. 16 July 2018 . en-GB. 2018-10-12.
  10. Web site: expert reaction to study looking at nutrient drink and prodromal Alzheimer's disease Science Media Centre. www.sciencemediacentre.org. en-US. 2018-10-12.
  11. News: Pharma giant ending Alzheimer's research. 2018. BBC News. 2018-10-12. en-GB.
  12. Web site: BBC Radio 4 - BBC Inside Science, Alzheimers research, Lucy in the Scanner, Smart bandages, From supernovae to Hollywood. BBC. en-GB. 2018-10-12.
  13. News: Tara Spires-Jones: the brain is complicated but funding research will bring progress The Centre for Dementia Prevention. 2016-12-02. The Centre for Dementia Prevention. 2018-10-12. en-US.
  14. News: How the Science Media Centre Helps Avoid Face-Palm Moments When Reading the News - Digital Science. 2015-09-01. Digital Science. 2018-10-12. en-GB.
  15. Web site: Tara Spires-Jones - Edinburgh Research Explorer. www.research.ed.ac.uk. en. 2018-10-10.
  16. Koffie . R. M., Hashimoto, T., Tai, H.-C., Kay, K. R., Serrano-Pozo, A., Joyner, D., Hou, S., Kopeikina, K. J., Frosch, M. P., Lee, V. M., Holtzman, D. M., Hyman, B. T., & Spires-Jones, T. L. . 2013 . Apolipoprotein E4 effects in Alzheimer's disease are mediated by synaptotoxic oligomeric amyloid-beta . . 135 . 7 . 2155–2168. 10.1093/brain/aws127. free . 22637583 . 3381721 .
  17. Colom-Cadena . M., Davies, C., Sirisi, S., Lee, J.-E., Simzer, E. M., Tzioras, M., Querol-Vilaseca, M., Sánchez-Aced, É., Chang, Y. Y., Holt, K., McGeachan, R. I., Rose, J., Tulloch, J., Wilkins, L., Smith, C., Andrian, T., Belbin, O., Pujals, S., Horrocks, M. H., Lleo, A., Spires-Jones, T. L. . 2023 . Synaptic oligomeric tau in Alzheimer's disease—A potential culprit in the spread of tau pathology through the brain . . 111 . 14 . 2170–2183. 10.1016/j.neuron.2023.04.020. free . 37192625 . 20.500.11820/fd5293ab-4c35-452e-8a3e-7d7dbc5fa29f . free .
  18. Kay . K. R., Smith, C., Wright, A. K., Serrano-Pozo, A., Pooler, A. M., Koffie, R., Bastin, M. E., Bak, T. H., Abrahams, S., Kopeikina, K. J., McGuone, D., Frosch, M. P., Gillingwater, T. H., Hyman, B. T., & Spires-Jones, T. L. . 2013 . Studying synapses in human brain with array tomography and electron microscopy . . 8 . 7 . 1366–1380 . 10.1038/nprot.2013.078 . 23787894 . 3712649 .
  19. News: CT1812. AlzForum . 2023-10-04. en.
  20. Santacruz. K., Lewis, J., Spires, T., Paulson, J., Kotilinek, L., Ingelsson, M., Guimaraes, A., DeTure, M., Ramsden, M., McGowan, E., Forster, C., Yue, M., Orne, J., Janus, C., Mariash, A., Kuskowski, M., Hyman, B., Hutton, M., & Ashe, K. H. . 2005 . Tau suppression in a neurodegenerative mouse model improves memory function . Science . 309 . 5733 . 476–481. 10.1126/science.1113694. 16020737 . 1574647 . 2005Sci...309..476S .
  21. de Calignon. A., Fox, L. M., Pitstick, R., Carlson, G. A., Bacskai, B. J., Spires-Jones, T. L., & Hyman, B. T. . 2010 . Caspase activation precedes and leads to tangles . Nature . 464 . 7292 . 1201–1204. 10.1038/nature08890. 20357768 . 3091360 . 2010Natur.464.1201D .
  22. de Calignon. A., Polydoro, M., Suárez-Calvet, M., William, C., Adamowicz, D. H., Kopeikina, K. J., Pitstick, R., Sahara, N., Ashe, K. H., Carlson, G. A., Spires-Jones, T. L., & Hyman, B. T. . 2012 . Propagation of tau pathology in a model of early Alzheimer's disease . Neuron . 73 . 4 . 685–697. 10.1016/j.neuron.2011.11.033. free . 22365544 . 3292759 .
  23. Web site: UK DRI: UK Dementia Research Institute UK DRI: UK Dementia Research Institute. 2018-10-12. UK DRI: UK Dementia Research Institute. en-gb. UK DRI: UK Dementia Research Institute. 2018-10-12.
  24. Colom-Cadena . M., Pegueroles, J., Herrmann, A. G., Henstridge, C. M., Muñoz, L., Querol-Vilaseca, M., Martín-Paniello, C. S., Luque-Cabecerans, J., Clarimon, J., Belbin, O., Núñez-Llaves, R., Blesa, R., Smith, C., McKenzie, C.-A., Frosch, M. P., Roe, A., Fortea, J., Andilla, J., Loza-Alvarez, P., Gelpi, E., Hyman, B. T., Spires-Jones, T. L.*, & Lleó, A. *. 2017 . Synaptic phosphorylated α-synuclein in dementia with Lewy bodies.. . 140 . 12 . 3204–3214. 10.1093/brain/awx275. free . 29177427. 5841145 .
  25. Jackson . R. J., Rose, J., Tulloch, J., Henstridge, C., Smith, C., & Spires-Jones, T. L. . 2019 . Clusterin accumulates in synapses in Alzheimer's disease and is increased in apolipoprotein E4 carriers . Brain Communications . fcz003 . 10.1093/braincomms/fcz003. free . 31853523 . 6904249 .
  26. Tzioras . M., Stevenson, A. J., Boche, D., & Spires-Jones, T. L. . 2020 . Microglial contribution to synaptic uptake in the prefrontal cortex in schizophrenia. . Neuropathology and Applied Neurobiology . 47 . 2 . 346–351 . 10.1111/nan.12660. free . 32892388 .

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