Coulson Lab - Neurotrophins in Alzheimer’s Disease

My lab is currently focusing on the reasons why cholinergic neurons of the basal forebrain die in Alzheimer’s disease, what contribution their loss makes to cognitive decline and whether manipulating neurotrophic signalling  (NGF, BDNF, TrkA/B, p75) can protect or restore cognitive function, and what role the neurotrophins play in the normal function of these neurons.

The lab is supported by:

  • National Health and Medical Research Council of Australia (NHMRC)
  • Clem Jones Centre for Aging Dementia Research (CJCADR)
  • Mason Foundation (Perpetual Trustees)

Staff

Students

  • Qian L, Milne MR, Shepheard S, Rogers ML, Medeiros R, Coulson EJ. (2018) Removal of p75 Neurotrophin Receptor Expression from Cholinergic Basal Forebrain Neurons Reduces Amyloid-β Plaque Deposition and Cognitive Impairment in Aged APP/PS1 Mice. Mol Neurobiol. 2018 Oct 29. doi: 10.1007/s12035-018-1404-2. [Epub ahead of print]
  • Lerch O, Pannek K, Laczó J, Nedelska Z, Fripp J, Hort J, Coulson E. (2018) Impairment of medial septal projections contributes to hippocampal atrophy in subjects at risk of Alzheimer’s Disease. Alzheimer's & Dementia: The Journal of the Alzheimer's Association 14 7: 1409-1410
  • Lerch O, Pannek K, Laczó J, Nedelska Z, Fripp J, Hort J, Coulson E. (2018) Impairment of basal forebrain projections contributes to hippocampal atrophy in subjects at risk of Alzheimer's disease. European Journal of Neurology 25: 380-380
  • Boskovic Z, Milne MR,  Qian L, Clifton HD, McGovern AE, Turnbull MT, Mazzone SB & Coulson EJ. (2018) Cholinergic basal forebrain neurons regulate fear extinction consolidation through p75 neurotrophin receptor signalling. Translation psychiatry 8 (1): 199. 21 September 2018 doi: 10.1038/s41398-018-0248-x.
  • Turnbull MT, Boskovic Z, Coulson EJ. (2018) Acute Down-regulation of BDNF Signaling Does Not Replicate Exacerbated Amyloid-β Levels and Cognitive Impairment Induced by Cholinergic Basal Forebrain Lesion. Frontiers in Molecular Neuroscience 11: 51. 22 February 2018 doi.org/10.3389/fnmol.2018.00051
  • May, Linda M., Anggono, Victor, Gooch, Helen M., Jang, Se E., Matusica, Dusan, Kerbler, Georg M., Meunier, Frederic A., Sah, Pankaj and Coulson, Elizabeth J. (2017) G-protein-coupled inwardly rectifying potassium (GIRK) channel activation by the p75 neurotrophin receptor is required for amyloid beta toxicity. Frontiers in Neuroscience11 455: . doi:10.3389/fnins.2017.00455
  • Coulson, Elizabeth J. and Bartlett, Perry F. (2017) An exercise path to preventing Alzheimer's disease : An Editorial Highlight on 'Exercise and BDNF reduce Ab production by enhancing alpha-secretase processing of APP'. Journal of Neurochemistry142 2: 191-193. doi:10.1111/jnc.14038
  • Turnbull, Marion T. and Coulson, Elizabeth J. (2017) Cholinergic basal forebrain lesion decreases neurotrophin signaling without affecting tau hyperphosphorylation in genetically susceptible mice. Journal of Alzheimer's Disease,55 3: 1141-1154. doi:10.3233/JAD-160805
  • Matusica, D., Alfonsi, F., Turner, B. J., Butler, T. J., Shepheard, S. R., Rogers, M. L., Skeldal, S., Underwood, CK., Mangelsdorf, M &  Coulson, E. J. (2016). Inhibition of motor neuron death in vitro and in vivo by a p75 neurotrophin receptor intracellular domain fragment. J Cell Sci, 129(3), 517-530. 
  • Kerbler, G. M., Nedelska, Z., Fripp, J., Laczo, J., Vyhnalek, M., Lisy, J., Hamlin, AS., Rose, S., Hort J. & Coulson, E. J. (2015). Basal Forebrain Atrophy Contributes to Allocentric Navigation Impairment in Alzheimer's Disease Patients. Front Aging Neurosci, 7, 185. 
  • Kerbler, G. M., Fripp, J., Rowe, C. C., Villemagne, V. L., Salvado, O., Rose, S. & Coulson, EJ. Alzheimer's Disease Neuroimaging, I. (2015). Basal forebrain atrophy correlates with amyloid beta burden in Alzheimer's disease. Neuroimage Clin, 7, 105-113. 
  • Coulson, E. J., & Andersen, O. M. (2015). The A-B-C for SORting APP. J Neurochem, 135(1), 1-3. 
  • Matusica, D., & Coulson, E. J. (2014). Local versus long-range neurotrophin receptor signalling: endosomes are not just carriers for axonal transport. Semin Cell Dev Biol, 31, 57-63. 
  • Edwards, S. R., Hamlin, A. S., Marks, N., Coulson, E. J., & Smith, M. T. (2014). Comparative studies using the Morris water maze to assess spatial memory deficits in two transgenic mouse models of Alzheimer's disease. Clin Exp Pharmacol Physiol, 41(10), 798-806. doi: 10.1111/1440-1681.12277
  • Boskovic, Z., Alfonsi, F., Rumballe, B. A., Fonseka, S., Windels, F., & Coulson, E. J. (2014). The role of p75NTR in cholinergic basal forebrain structure and function. J Neurosci, 34(39), 13033-13038. doi: 10.1523/JNEUROSCI.2364-14.2014
  • D Matusica, S Skeldal, AM Sykes, N Palstra, A Sharma, EJ Coulson (2013) An intracellular domain fragment of the p75 neurotrophin receptor enhances TrkA receptor function. Journal of Biological Chemistry 288:11144-54.

We are currently recruiting Honours and HDR students for projects relating to Alzheimer’s Disease, including those mentioned below. We are particularly keen to recruit a student for Project 2, preferably with electrophysiology experience. Please send your CV to Bree Rumballe b.rumballe@uq.edu.au for review.

  • Project 1: The role of cleavage of p75 neurotrophin receptor in neurotrophic function (cell biology)
  • Project 2: The role of neurotrophins in regulating the synaptic function of cholinergic basal forebrain neurons (mouse studies: electrophysiology, behaviour, fMRI, in vivo genetic manipulation)
  • Project 3: Studying basal forebrain function in Alzheimer’s disease and sleep apnea (human MRI and PET analysis)
  • Project 4: Developing optimised peptides for treating neurotrophic dysfunction in neurodegenerative disease (biochemistry)

Sleep apnea study

Professor Coulson’s team are researching what factors makes sleep disruption a risk factor for Alzheimer's disease. They are beginning a study that will follow patients aged 55 to 75 with sleep apnoea over an extended period, to determine whether using a continuous positive airway pressure (CPAP) ventilator, which keeps airways open during sleep, protects against brain degeneration and lowers the risk of dementia.

See the flyer for more information regarding the clinical trial and/or email coulsontrials@uq.edu.au

Sterling's Dream

Professor Coulson and colleagues, Dr Eamon Eeles (The Prince Charles Hospital) and Professor Stephen Rose (CSIRO), are involved in research studying what factors make the gold standard drugs for Alzheimer's disease more likely to be effective. Information on this study (Sterling’s Dream) can be found here

Find out more about our research environment and how to apply to do a short or long-term research project with us.