Tara Spires-Jones

Last updated
Tara L Spires-Jones, DPhil, FMedSci
Tara-headshotDRI.jpg
2019 by Sparatires
Born
Tara Spires
Alma materUniversity of Texas at Austin University of Oxford
Known forResearching mechanisms of synapse degeneration in Alzheimer’s disease.
Scientific career
FieldsNeuroscience
InstitutionsMassachusetts General Hospital

Harvard Medical School

University of Edinburgh
Thesis Genetic and epigenetic interactions in activity-dependent cortical plasticity.  (2003)

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

Contents

Tara-headshotDRI.jpg

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. [2] [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. [2] 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, [2] 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] In 2024, Prof Spires-Jones was elected a Fellow of the UK Academy of Medical Sciences.

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 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]

Personal life


As well as her academic career, Spires-Jones is also a member of the University of Edinburgh’s Acapella group. She is a tenor.

Related Research Articles

<span class="mw-page-title-main">Frontotemporal dementia</span> Types of dementia involving the frontal or temporal lobes

Frontotemporal dementia (FTD), also called frontotemporal degeneration disease or frontotemporal neurocognitive disorder, encompasses several types of dementia involving the progressive degeneration of the brain's frontal and temporal lobes. FTD is the second most prevalent type of early onset dementia after Alzheimer's disease. Men and women appear to be equally affected. FTD generally presents as a behavioral or language disorder with gradual onset. Signs and symptoms tend to appear in late adulthood, typically between the ages of 45 and 65, although it can affect people younger or older than this. Currently, no cure or approved symptomatic treatment for FTD exists, although some off-label drugs and behavioral methods are prescribed.

<span class="mw-page-title-main">Tau protein</span> Group of six protein isoforms produced from the MAPT gene

The tau proteins form a group of six highly soluble protein isoforms produced by alternative splicing from the gene MAPT. They have roles primarily in maintaining the stability of microtubules in axons and are abundant in the neurons of the central nervous system (CNS), where the cerebral cortex has the highest abundance. They are less common elsewhere but are also expressed at very low levels in CNS astrocytes and oligodendrocytes.

<span class="mw-page-title-main">Frontotemporal lobar degeneration</span> Atrophy of the brains frontal and temporal lobes

Frontotemporal lobar degeneration (FTLD) is a pathological process that occurs in frontotemporal dementia. It is characterized by atrophy in the frontal lobe and temporal lobe of the brain, with sparing of the parietal and occipital lobes.

<span class="mw-page-title-main">Neurofibrillary tangle</span> Aggregates of tau protein known as a biomarker of Alzheimers disease

Neurofibrillary tangles (NFTs) are intracellular aggregates of hyperphosphorylated tau protein that are most commonly known as a primary biomarker of Alzheimer's disease. Their presence is also found in numerous other diseases known as tauopathies. Little is known about their exact relationship to the different pathologies.

<span class="mw-page-title-main">Tauopathy</span> Medical condition

Tauopathies are a class of neurodegenerative diseases characterized by the aggregation of abnormal tau protein. Hyperphosphorylation of tau proteins causes them to dissociate from microtubules and form insoluble aggregates called neurofibrillary tangles. Various neuropathologic phenotypes have been described based on the anatomical regions and cell types involved as well as the unique tau isoforms making up these deposits. The designation 'primary tauopathy' is assigned to disorders where the predominant feature is the deposition of tau protein. Alternatively, diseases exhibiting tau pathologies attributed to different and varied underlying causes are termed 'secondary tauopathies'. Some neuropathologic phenotypes involving tau protein are Alzheimer's disease, frontotemporal dementia, progressive supranuclear palsy, and corticobasal degeneration.

<span class="mw-page-title-main">Neurodegenerative disease</span> Central nervous system disease

A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their death. Neurodegenerative diseases include amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, multiple system atrophy, tauopathies, and prion diseases. Neurodegeneration can be found in the brain at many different levels of neuronal circuitry, ranging from molecular to systemic.Because there is no known way to reverse the progressive degeneration of neurons, these diseases are considered to be incurable; however research has shown that the two major contributing factors to neurodegeneration are oxidative stress and inflammation. Biomedical research has revealed many similarities between these diseases at the subcellular level, including atypical protein assemblies and induced cell death. These similarities suggest that therapeutic advances against one neurodegenerative disease might ameliorate other diseases as well.

<span class="mw-page-title-main">Synapse</span> Structure connecting neurons in the nervous system

In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another neuron or to the target effector cell.

The biochemistry of Alzheimer's disease, the most common cause of dementia, is not yet very well understood. Alzheimer's disease (AD) has been identified as a proteopathy: a protein misfolding disease due to the accumulation of abnormally folded amyloid beta (Aβ) protein in the brain. Amyloid beta is a short peptide that is an abnormal proteolytic byproduct of the transmembrane protein amyloid-beta precursor protein (APP), whose function is unclear but thought to be involved in neuronal development. The presenilins are components of proteolytic complex involved in APP processing and degradation.

<span class="mw-page-title-main">Alzheimer's disease</span> Progressive neurodegenerative disease

Alzheimer's disease (AD) is a neurodegenerative disease that usually starts slowly and progressively worsens, and is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems with language, disorientation, mood swings, loss of motivation, self-neglect, and behavioral issues. As a person's condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the average life expectancy following diagnosis is three to twelve years.

Transneuronal degeneration is the death of neurons resulting from the disruption of input from or output to other nearby neurons. It is an active excitotoxic process when a neuron is overstimulated by a neurotransmitter causing the dysfunction of that neuron which drives neighboring neurons into metabolic deficit, resulting in rapid, widespread loss of neurons. This can be either anterograde or retrograde, indicating the direction of the degeneration relative to the original site of damage. There are varying causes for transneuronal degeneration such as brain lesions, disconnection syndromes, respiratory chain deficient neuron interaction, and lobectomies. Although there are different causes, transneuronal degeneration generally results in the same effects to varying degrees. Transneuronal degeneration is thought to be linked to a number of diseases, most notably Huntington's disease and Alzheimer's disease, and researchers recently have been performing experiments with monkeys and rats, monitoring lesions in different parts of the body to study more closely how exactly the process works.

<span class="mw-page-title-main">Synaptopathy</span> Medical condition

A synaptopathy is a disease of the brain, spinal cord or peripheral nervous system relating to the dysfunction of synapses. This can arise as a result of a mutation in a gene encoding a synaptic protein such as an ion channel, neurotransmitter receptor, or a protein involved in neurotransmitter release. It can also arise as a result of an autoantibody targeting a synaptic protein. Synaptopathies caused by ion channel mutations are also known as synaptic channelopathies. An example is episodic ataxia. Myasthenia gravis is an example of an autoimmune synaptopathy. Some toxins also affect synaptic function. Tetanus toxin and botulinum toxin affect neurotransmitter release. Tetanus toxin can enter the body via a wound, and botulinum toxin can be ingested or administered therapeutically to alleviate dystonia or as cosmetic treatment.

<span class="mw-page-title-main">Cholinergic neuron</span> Type of nerve cell

A cholinergic neuron is a nerve cell which mainly uses the neurotransmitter acetylcholine (ACh) to send its messages. Many neurological systems are cholinergic. Cholinergic neurons provide the primary source of acetylcholine to the cerebral cortex, and promote cortical activation during both wakefulness and rapid eye movement sleep. The cholinergic system of neurons has been a main focus of research in aging and neural degradation, specifically as it relates to Alzheimer's disease. The dysfunction and loss of basal forebrain cholinergic neurons and their cortical projections are among the earliest pathological events in Alzheimer's disease.

Primary age-related tauopathy (PART) is a neuropathological designation introduced in 2014 to describe the neurofibrillary tangles (NFT) that are commonly observed in the brains of normally aged and cognitively impaired individuals that can occur independently of the amyloid plaques of Alzheimer's disease (AD). The term and diagnostic criteria for PART were developed by a large group of neuropathologists, spearheaded by Drs. John F. Crary and Peter T. Nelson. Despite some controversy, the term PART has been widely adopted, with the consensus criteria cited over 1130 times as of April 2023 according to Google Scholar.

Beth Stevens is an associate professor in the Department of Neurology at Harvard Medical School and the F. M. Kirby Neurobiology Center at Boston Children’s Hospital. She has helped to identify the role of microglia and complement proteins in the "pruning" or removal of synaptic cells during brain development, and has also determined that the impaired or abnormal microglial function could be responsible for diseases like autism, schizophrenia, and Alzheimer's.

<span class="mw-page-title-main">Virginia Man-Yee Lee</span> American neuroscientist and biochemist

Virginia Man-Yee Lee is a Chinese-born American biochemist and neuroscientist who specializes in the research of Alzheimer's disease. She is the current John H. Ware 3rd Endowed Professor in Alzheimer's Research at the Department of Pathology and Laboratory Medicine, and the director of the Center for Neurodegenerative Disease Research and co-director of the Marian S. Ware Alzheimer Drug Discovery Program at the Perelman School of Medicine, University of Pennsylvania. She received the 2020 Breakthrough Prize in Life Sciences.

The neuroscience of aging is the study of the changes in the nervous system that occur with ageing. Aging is associated with many changes in the central nervous system, such as mild atrophy of the cortex that is considered non-pathological. Aging is also associated with many neurological and neurodegenerative disease such as amyotrophic lateral sclerosis, dementia, mild cognitive impairment, Parkinson's disease, and Creutzfeldt–Jakob disease.

Corticobasal syndrome (CBS) is a rare, progressive atypical Parkinsonism syndrome and is a tauopathy related to frontotemporal dementia. CBS is typically caused by the deposit of tau proteins forming in different areas of the brain.

<span class="mw-page-title-main">David M. Holtzman</span> Medical researcher

David M. Holtzman is an American physician-scientist known for his work exploring the biological mechanisms underlying neurodegeneration, with a focus on Alzheimer's disease. Holtzman is former Chair of the Department of Neurology, Scientific Director of the Hope Center for Neurological Disorders, and associate director of the Knight Alzheimer's Disease Research Center at Washington University School of Medicine in St. Louis, Missouri. Holtzman's lab is known for examining how apoE4 contributes to Alzheimer's disease as well as how sleep modulates amyloid beta in the brain. His work has also examined the contributions of microglia to AD pathology.

<span class="mw-page-title-main">Experimental models of Alzheimer's disease</span>

Experimental models of Alzheimer's disease are organism or cellular models used in research to investigate biological questions about Alzheimer's disease as well as develop and test novel therapeutic treatments. Alzheimer's disease is a progressive neurodegenerative disorder associated with aging, which occurs both sporadically or due to familial passed mutations in genes associated with Alzheimer's pathology. Common symptoms associated with Alzheimer's disease include: memory loss, confusion, and mood changes.

<span class="mw-page-title-main">A. David Smith</span>

Anthony David Smith FMedSci is a British biochemist and pharmacologist. Smith has spent his entire academic career in the University of Oxford. His research focuses on biochemical changes with disease and prevention. This includes co-founding the Oxford Project to Investigate Memory and Ageing (OPTIMA). He is one of the leaders of international research to find ways to prevent dementia. He is also known for his work on the anatomical neuropharmacology of the basal ganglia.

References

  1. ↑ "Prof Tara Spires-Jones". The University of Edinburgh. Retrieved 2018-10-09.
  2. 1 2 3 4 Office, FENS. "Tara SPIRES-JONES". FENS.org. Retrieved 2018-10-09.
  3. ↑ "Professor Tara Spires-Jones | The Scottish Science Advisory Council". www.scottishscience.org.uk. Retrieved 2018-10-09.
  4. ↑ "Scientist Focus: Dr Tara Spires-Jones | Alzheimer's Research UK Blog". www.dementiablog.org. Retrieved 2018-10-10.
  5. ↑ "Professor Tara Spires-Jones | The Scottish Science Advisory Council". www.scottishscience.org.uk. Retrieved 2018-10-10.
  6. ↑ "Brain Communications" . Retrieved 2023-10-04.
  7. ↑ "ANNOUNCING OUR NEW BNA PRESIDENT-ELECT: TARA SPIRES-JONES". British Neuroscience Association. 2021-04-15. Retrieved 2023-10-04.
  8. ↑ "NCTalks with Tara Spires-Jones: ApoE4, synapse degeneration and Alzheimer's - Neuro Central". Neuro Central. 2018-04-09. Retrieved 2018-10-12.
  9. ↑ "Long Interview: Tara Spires-Jones, 14/07/2018, Good Morning Scotland - BBC Radio Scotland". BBC. 16 July 2018. Retrieved 2018-10-12.
  10. ↑ "expert reaction to study looking at nutrient drink and prodromal Alzheimer's disease | Science Media Centre". www.sciencemediacentre.org. Retrieved 2018-10-12.
  11. ↑ "Pharma giant ending Alzheimer's research". BBC News. 2018. Retrieved 2018-10-12.
  12. ↑ "BBC Radio 4 - BBC Inside Science, Alzheimers research, Lucy in the Scanner, Smart bandages, From supernovae to Hollywood". BBC. Retrieved 2018-10-12.
  13. ↑ "Tara Spires-Jones: the brain is complicated but funding research will bring progress | The Centre for Dementia Prevention". The Centre for Dementia Prevention. 2016-12-02. Retrieved 2018-10-12.
  14. ↑ "How the Science Media Centre Helps Avoid Face-Palm Moments When Reading the News - Digital Science". Digital Science. 2015-09-01. Retrieved 2018-10-12.
  15. ↑ "Tara Spires-Jones - Edinburgh Research Explorer". www.research.ed.ac.uk. Retrieved 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". Brain . 135 (7): 2155–2168. doi: 10.1093/brain/aws127 . PMC   3381721 . PMID   22637583.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  17. 1 2 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". Neuron . 111 (14): 2170–2183. doi: 10.1016/j.neuron.2023.04.020 . hdl: 20.500.11820/fd5293ab-4c35-452e-8a3e-7d7dbc5fa29f . PMID   37192625.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  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". Nature Protocols . 8 (7): 1366–1380. doi:10.1038/nprot.2013.078. PMC   3712649 . PMID   23787894.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  19. ↑ "CT1812". AlzForum. Retrieved 2023-10-04.
  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. Bibcode:2005Sci...309..476S. doi:10.1126/science.1113694. PMC   1574647 . PMID   16020737.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  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. Bibcode:2010Natur.464.1201D. doi:10.1038/nature08890. PMC   3091360 . PMID   20357768.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  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. doi: 10.1016/j.neuron.2011.11.033 . PMC   3292759 . PMID   22365544.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  23. ↑ "UK DRI: UK Dementia Research Institute | UK DRI: UK Dementia Research Institute". UK DRI: UK Dementia Research Institute. UK DRI: UK Dementia Research Institute. 2018-10-12. Retrieved 2018-10-12.{{cite web}}: CS1 maint: others (link)
  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". Brain . 140 (12): 3204–3214. doi: 10.1093/brain/awx275 . PMC   5841145 . PMID   29177427.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  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. doi: 10.1093/braincomms/fcz003 . PMC   6904249 . PMID   31853523.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  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. doi: 10.1111/nan.12660 . PMID   32892388.{{cite journal}}: CS1 maint: multiple names: authors list (link)
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.