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6 October 2022

2022 CANTAB Research Grant: Examining the relationship between BDNF and Parkinson’s Disease

Amy Tiberio was one of the winners of the 2022 CANTABTM Research Grant. Here she explains more about her project and what winning this grant means for her.

I would first like to thank Cambridge Cognition for selecting my research for the competitive and prestigious 2022 CANTABTM Research Grant. I would also like to extend my thanks to the team from Cambridge Cognition, Emily, Louise and Laura, who have been so helpful in getting me started with CANTABTM. Finally, I would like to thank ParkC  (http://parkc.co) and CHIRI (Curtin Health Innovation Research Institute) for their continued support of my research.

My name is Amy Tiberio, and I am a PhD student, Research Assistant and Sessional Academic at Curtin University. I am also the Chairperson of a local independent school Board and a full time Mum. I started formulating the idea for this research project in 2019, inspired by my interest in neuroplasticity and my grandfather Sandrino’s Parkinson’s diagnosis.

I am very excited about the prospect of adding to the existing body of Parkinson’s disease research, which I hope will contribute to improving the lives and outcomes of people living with the disease.

What is the project about and why is this important?

Parkinson’s Disease (PD) is a debilitating neurodegenerative disorder, affecting an estimated 8.5 million people worldwide1. Presentation of the disease can vary widely, but the most identifiable symptom is movement impairment, caused by the progressive and irreversible loss of dopamine-producing cells in the substantia nigra2,3. Primary treatment involves oral doses of the dopamine precursor levodopa, which works to replenish missing dopamine and restore motor function4. As the disease progresses and more dopamine producing neurons die, levodopa becomes increasingly ineffective at replacing dopamine loss and treatment becomes palliative, shifting towards improving quality of life1,4

The Brain Derived Neurotrophic Factor (BDNF) is a neuroplastic growth protein believed to underpin a range of cognitive processes5, including memory and learning5,6. Dysfunctions in BDNF upregulation have also been noted in a wide range of mood and neurological disorders7,8, including Alzheimer’s disease9 and depression10. Animal studies have identified BDNF as crucial to the development, maintenance and survival of dopamine producing neurons in the mammalian substantia nigra11,12 and preliminary research suggests circulatory BDNF is impacted in the human Parkinson's disease brain13. These findings have generated significant interest in BDNF as a potential therapeutic target for dopaminergic rescue and regeneration in PD14,15, but the supporting literature is scarce and inconsistent16,17.

A review of PD BDNF literature uncovered widespread methodological issues16,17, including lack of appropriate screening protocols, use of inappropriate or non-recommended tests to measure variables, and the use of underpowered and/or convenience sampling16,17. The review also found studies typically only measure BDNF changes across one dichotomous variable: does the patient have a PD diagnosis or not? In doing so, these studies fail to assess the impact of Parkinson-specific variables and symptoms on BDNF levels, including potential confounds related to medication use, severity of motor impairment1,2, comorbid diseases such as Alzheimer’s disease9 and depression10, and the presence and/or severity of any cognitive impairment5,6.

My project aims to understand more about the potential of BDNF as a therapeutic target in PD. It will be the first large cohort study to measure changes in BDNF serum levels across a wide spectrum of Parkinsonian symptoms, including the different stages and characteristics of motor impairment18, and profiles of cognitive impairment19. The study will also aim to address previous methodological issues16,17, generating a more complete and accurate picture of the relationship between PD and BDNF. To achieve this, I will be recruiting a sample of 120 participants with a clinical diagnosis of Parkinson’s disease. Each participant will undertake a cognitive testing session at their house, followed by a motor assessment on site at Curtin. When participants visit Curtin for their motor assessment, we will also draw a blood sample to measure their BDNF.

What CANTABTM tests will you use and why?

Given the prevalence of impairment in Parkinson’s disease and the important role BDNF plays in healthy cognition5, measuring cognitive performance is a key variable in this research. To assess cognitive impairment in Parkinson’s disease, the Movement Disorder Society19 recommends the following CANTABTM tests for use in each cognitive domain: for attention and working memory, we will be using the Match to Sample Visual Search (MTS) and Digit Span (DGS) task; for executive function, we will use Stockings of Cambridge (SOC); for the memory domain, we will be using the Verbal Recognition Memory (VRM) test; and for capturing visuospatial ability, we will be using the Spatial Working Memory (SWM) task. In addition to these cognitive domains, our study will also aim to capture information about patient’s impulsivity and inhibition using the Cambridge Gambling Task (CGT), Stop Signal Task (SST), and the Emotional Recognition Task (ERT).  While this will be my first time using CANTABTM, the software is used by my supervisors and their research collective ParkC in all their Parkinson’s research and comes highly recommended.

How important was funding from Cambridge Cognition for your work?

As a PhD student with a limited research budget, I was absolutely thrilled to receive this grant. It has given me the opportunity to incorporate additional tests and measure new variables that I would not have had the funding to include previously. It will also allow me to undertake researcher phlebotomy training. BDNF levels are measured in blood serum and this training will allow me to collect and process the samples myself, eliminating any additional costs and time constraints that come with engaging an external pathology company. .

References

1. World Health Organisation. (2022, June 13). Parkinson’s Disease Fact Sheet. Retrieved from https://www.who.int/news-room/fact-sheets/detail/parkinson-disease.

2. Jankovic, J. (2007). Parkinson’s disease: clinical features and diagnosis. Journal of Neurology, Neurosurgery and Psychiatry, 79, 368-376. doi:10.1136/jnnp.2007.131045

3. Parker, P. R. L., Lalive, A. L., & Kreitzer, A. C. (2016). Pathway-Specific Remodeling of Thalamostriatal Synapses in Parkinsonian Mice. Neuron, 89(4), 734-740. doi:10.1016/j.neuron.2015.12.038

4. Katzenschlager, R., & Lees, A. J. (2002). Treatment of Parkinson’s disease: levodopa as the first choice. Journal of Neurology, 249(2), 19-24. doi:10.1007/s00415-002-1204-4

5. Lu, B., Nagappan, G., & Lu, Y. (2014). BDNF and synaptic plasticity, cognitive function, and dysfunction. Handbook of experimental pharmacology, 220, 223–250. doi:10.1007/978-3-642-45106-5_9

6. Sasi, M., Vignoli, B., Canossa, M., & Blum, R. (2017). Neurobiology of local and intercellular BDNF signalling. European Journal of Physiology, 469, 593-610. doi:10.1007/s00424-017-1964-4

7. Hashimoto, K. (2010). Brain-derived neurotrophic factor as a biomarker for mood disorders: An historical overview and future directions. Psychiatry and Clinical Neurosciences, 64(4), 341-357. doi:https://doi.org/10.1111/j.1440-1819.2010.02113.x

8. Zuccato, C., & Cattaneo, E. (2009). Brain-derived neurotrophic factor in neurodegenerative diseases. Nature Reviews Neurology, 5(6), 311-322. doi:https://doi.org/10.1038/nrneurol.2009.54

9. Ng, T. K. S., Ho, C. S. H., Tam, W. W. S., Kua, E. H., & Ho, R. C. M. (2019). Decreased serum brain-derived neurotrophic factor (BDNF) levels in patients with Alzheimer’s disease (AD): A systematic review and meta-analysis. International Journal of Molecular Sciences, 20(2), Article 257. doi:https://doi.org/10.3390/ijms20020257

10. Karege, F., Perret, G., Bondolfi, G., Schwald, M., Bertschy, G., & Aubry, J. M. (2002). Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Research, 109(2), 143-148. doi:https://doi.org/10.1016/S0165-1781(02)00005-7

11. Baquet, Z. C., Bickford, P. C., & Jones, K. R. (2005). Brain-derived neurotrophic factor is required for the establishment of the proper number of dopaminergic neurons in the substantia nigra pars compacta. The Journal of Neuroscience, 25(26), 6251-6259. doi:10.1523/JNEUROSCI.4601-04.2005

12. Porritt, M. J., Batchelor, P. E., & Howells, D. W. (2005). Inhibiting BDNF expression by antisense oligonucleotide infusion causes loss of nigral dopaminergic neurons. Experimental neurology, 192, 226-234. doi:10.1016/j.expneurol.2004.11.030

13. Ziebell, M., Khalid, U., Klein, A. B., Aznar, S., Thomsen, G., Jensen, P., & Knudsen, G. M. (2012). Striatal dopamine transporter binding correlates with serum BDNF levels in patients with striatal dopaminergic neurodegeneration. Neurobiology of Aging, 33, 428.e1-428.e5. doi:10.1016/j.neurobiolaging.2010.11.010

14. Palaz, E., Wysocka, A., Gasiorowska, A., Chalimoniuk, M., Niewiadomski, W., & Niewiadomska, G. (2019). BDNF as a promising therapeutic agent in Parkinson’s Disease. International Journal of Molecular Sciences, 21, 1-23. doi:10.3390/ijms21031170

15. Fumagalli, F., Racagni, G., & Riva, M. A. (2006). Shedding light into the role of BDNF in the pharmacotherapy of Parkinson’s disease. The Pharmacogenomics Journal, 6, 95-104. doi:10.1038/sj.tpj.6500360.

16. Jiang, L., Zhang, H., Wang, C., Ming, F., Shi, X., & Yang, M. (2019). Serum level of brain-derived neurotrophic factor in Parkinson’s disease: A meta-analysis. Progress in Neuropsychopharmacology & Biological Psychiatry, 88, 168-174. doi:10.1016/j.pnpbp.2018.07.010

17. Rahmani, F., Saghazadeh, A., Rahmani, M., Teixeira, A. L., Rezaei, N., Aghamollaii, V., & Ardebili, H. E. (2019). Plasma levels of brain-derived neurotrophic factor in patients with Parkinson’s disease: A systematic review and meta-analysis. Brain Research, 1704, 127-136. doi:10.1016/j.brainres.2018.10.006

18. Postuma, R. B., Berg, D., Stern, M., Poewe, W., Olanow, C. W., Oertel, W., Obeso, J., Marek, K., Litvan, I., Lang, A. E., Halliday, G., Goetz, C. G., Gasser, T., Dubois, B., Chan, P., Bloem, B. R., Adler, C. H., & Deuschl, G. (2015). MDS clinical diagnostic criteria for Parkinson's disease. Movement Disorders, 30(12), 1591-1601. doi:https://doi.org/10.1002/mds.26424

19. Litvan, I., Goldman, J. G., Tröster, A. I., Schmand, B. A., Weintraub, D., Petersen, R. C., Mollenhauer, B., Adler, C. H., Marder, K., Williams-Gray, C. H., Aarsland, D., Kulisevsky, J., Rodriguez-Oroz, M. C., Burn, D. J., Barker, R. A., & Emre, M. (2012). Diagnostic criteria for mild cognitive impairment in Parkinson's disease: Movement Disorder Society Task Force guidelines. Movement Disorders, 27(3), 349-356. doi:https://doi.org/10.1002/mds.24893

Tags : cantab | cantab testimonial | cantab research grant | parkinson's disease

Author portrait

Amy Tiberio, Curtin University.