Tara Spires-Jones

Lab Members
Chris Henstridge (Postdoc)
Abi Herrmann (Postdoc)
Rosie Jackson (PhD Student)
Ellie Pickett (PhD Student)


Dr. Tara Spires-Jones
Reader and Chancellor's Fellow
Tel: +44(0) 131 651 1895


Lab Webpage

E-mail: ccns@ed.ac.uk

Research Interests
My research focuses on the mechanisms and reversibility of neuronal degeneration in Alzheimer’s disease and ageing.  We hypothesize that the degeneration of synapses, the connections between neuronal cells in the brain, causes memory impairments and that targeting the proteins that cause synaptic degeneration will allow recovery of cognitive function. Previous work from our group has shown that both of the proteins involved in the neuropathological lesions in Alzheimer’s (amyloid beta and tau) contribute to synapse loss in Alzheimer’s disease, and further that reducing the levels of soluble amyloid beta or tau prevents synaptic degeneration and improves memory in disease models. These experiments indicate that the plasticity of synapses will allow recovery after treatments, giving hope for some functional recovery in patients if we can develop therapies that remove the toxic protein species from the brain.

For our experiments, we apply high-resolution imaging techniques, including multiphoton imaging and array tomography, to examine the structure and function of synapses in healthy and diseased brain.  Multiphoton microscopy allows imaging of synapses over time to determine the time-course of disease processes and allows for imaging the brain before and after treatments to test candidate therapeutics.  Array tomography is a post-mortem imaging technique involving high-throughput imaging of thousands of synapses to determine whether disease-related proteins are associated with synapse shrinkage and loss.  We have accumulated the world’s first brain bank of human tissue prepared for the array tomography technique, which we are using to investigate the relationship between synaptic changes and dementia.

Key Publications
Henstridge CM, Jackson RJ, Kim JM, Herrmann AG, Wright AK, Harris SE, Bastin ME, Starr JM, Wardlaw J, Gillingwater TH, Smith C, McKenzie CA, Cox SR, Deary IJ, Spires-Jones TL. 2015. Post-mortem brain analyses of the Lothian Birth Cohort 1936: extending lifetime cognitive and brain phenotyping to the level of the synapse. Acta neuropathologica communications 3(1):53. (http://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-015-0232-0 )
Spires-Jones TL and Hyman BT. (2014) The Intersection of Amyloid Beta and Tau at Synapses in Alzheimer's Disease Neuron 82: 756­771.
Kay KR, Smith C, Wright AK, Serrano-Pozo A, Pooler AM, Koffie R, Bastin ME, Bak TH, Abrahams S, Kopeikina KJ, McGuone D, Frosch MP, Gillingwater TH, Hyman BT and Spires-Jones TL. (2013) Studying synapses in human brain with array tomography and electron microscopy. Nature protocols, 8(7):1366-80.
Kopeikina KJ, Wegmann S, Pitstick R, Carlson GA, Bacskai BJ, Betensky RA, Hyman BT and Spires-Jones TL. (2013) Tau causes synapse loss without disrupting calcium homeostasis in the rTg4510 model of tauopathy. PLoS One, 8(11):e80834.
Koffie RM, Hashimoto T, Tai HC, Kay KR, Serrano-Pozo A, Joyner D, Hou S, Kopeikina KJ, Frosch MP, Lee VM, Holtzman DM, Hyman BT and Spires-Jones TL. (2012) Apolipoprotein E4 effects in Alzheimer's disease are mediated by synaptotoxic oligomeric amyloid-beta. Brain : a journal of neurology, 135(Pt 7):2155-68.
de Calignon A, Fox LM, Pitstick R, Carlson GA, Bacskai BJ, Spires-Jones TL and Hyman BT. (2010) Caspase activation precedes and leads to tangles. Nature, 464(7292):1201-4.
Koffie RM, Meyer-Luehmann M, Hashimoto T, Adams KW, Mielke ML, Garcia-Alloza M, Micheva KD, Smith SJ, Kim ML, Lee VM, Hyman BT and Spires-Jones TL. (2009) Oligomeric amyloid beta associates with postsynaptic densities and correlates with excitatory synapse loss near senile plaques. Proc Natl Acad Sci U S A., 106(10):4012-7.
Full details of publications can be found here.

Funding Sources
Alzheimer's Research UK; Scottish government's Chief Scientist Office

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