Tara Spires-Jones

Last updated
Tara Spires-Jones
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 deputy director of the Centre for Discovery Brain Sciences at the University of Edinburgh. [1] She is also a group leader in the UK Dementia Research Institute.

Contents

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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]

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]

Related Research Articles

<span class="mw-page-title-main">Glia</span> Support cells in the nervous system

Glia, also called glial cells(gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. The neuroglia make up more than one half the volume of neural tissue in our body. They maintain homeostasis, form myelin in the peripheral nervous system, and provide support and protection for neurons. In the central nervous system, glial cells include oligodendrocytes, astrocytes, ependymal cells and microglia, and in the peripheral nervous system they include Schwann cells and satellite cells.

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

Frontotemporal dementia (FTD), or frontotemporal degeneration disease, or frontotemporal neurocognitive disorder, encompasses several types of dementia involving the progressive degeneration of frontal and temporal lobes. FTDs broadly present as behavioral or language disorders with gradual onsets. Common signs and symptoms include significant changes in social and personal behavior, apathy, blunting of emotions, and deficits in both expressive and receptive language. Currently, there is no cure for FTD, but there are treatments that help alleviate symptoms.

<span class="mw-page-title-main">Progressive supranuclear palsy</span> Medical condition

Progressive supranuclear palsy (PSP) is a late-onset neurodegenerative disease involving the gradual deterioration and death of specific volumes of the brain. The condition leads to symptoms including loss of balance, slowing of movement, difficulty moving the eyes, and cognitive impairment. PSP may be mistaken for other types of neurodegeneration such as Parkinson's disease, frontotemporal dementia and Alzheimer's disease. The cause of the condition is uncertain, but involves the accumulation of tau protein within the brain. Medications such as levodopa and amantadine may be useful in some cases.

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

The tau proteins are 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> Medical condition

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

Tauopathy belongs to a class of neurodegenerative diseases involving the aggregation of tau protein into neurofibrillary or gliofibrillary tangles in the human brain. Tangles are formed by hyperphosphorylation of the microtubule protein known as tau, causing the protein to dissociate from microtubules and form insoluble aggregates. The mechanism of tangle formation is not well understood, and whether tangles are a primary cause of Alzheimer's disease or play a peripheral role is unknown.

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

A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell 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.

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 typical life expectancy following diagnosis is three to nine 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.

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 . 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)
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