Abstract 2437 Neuroplasticity in Alzheimer's Treatment: The Impact of Psychedelic-Induced TrkB Activation

Alzheimer's Disease (AD) is one of the most debilitating forms of dementia,1 characterized by the gradual deterioration of cognitive functions such as memory, comprehension, language, reasoning, and judgment.2 AD accounts for two out of three dementia cases in people aged 65 years and older.2 One of the first clear pathological signs of AD is synaptic dysfunction,1 which is associated with subsequent neuronal degeneration.1 Neuroplasticity, the brain's ability to make new synaptic connections, could compensate for the pathology of AD and is a potential target for AD treatment.3 Tyrosine receptor kinase B (TrkB) proteins are brain-derived neurotrophic factor (BDNF) receptors that play a crucial role in neuroplasticity, due to the fact that activating the BDNF-TrkB pathway results in the creation of new synapses.4 Interestingly, some psychedelics, including (LSD) and (PSI), have been shown to increase neuroplasticity by binding to TrkB and assisting the binding of BDNF to the TrkB receptors.5 The Governor's Academy SMART team investigated TrkB's mechanism of BDNF binding and molecular interaction with LSD and PSI. With support from 3D Molecular Designs, we designed and printed a 3D model that highlights regions of TrkB important to BDNF binding and areas crucial to interaction with psychedelics. Continued research on these interactions may lead to the development of newer and more effective treatments for AD, potentially including chemicals that mimic the effects of psychedelics.1 1 Koch, G., & Spampinato, D. (2022). Alzheimer disease and neuroplasticity. Handbook of clinical neurology, 184, 473 479. https://doi.org/10.1016/B978-0-12-819410-2.00027-8 2 Kumar, A., Sidhu, J., Goyal, A., & Tsao, J. W. (2022). Alzheimer Disease. In StatPearls. StatPearls Publishing.] 3 Colavitta, M. F., & Barrantes, F. J. (2023). Therapeutic Strategies Aimed at Improving Neuroplasticity in Alzheimer Disease. Pharmaceutics, 15(8), 2052. https://doi.org/10.3390/pharmaceutics15082052 4 Meng, L., Liu, B., Ji, R., Jiang, X., Yan, X., & Xin, Y. (2019). Targeting the BDNF/TrkB pathway for the treatment of tumors. Oncology letters, 17(2), 2031-2039. https://doi.org/10.3892/o1.2018.9854 5 Moliner, R., Girych, M., Brunello, C. A., Kovaleva, V., Biojone, C., Enkavi, G., Antenucci, L., Kot, E. F., Goncharuk, S. A., Kaurinkoski, K., Kuutti, M., Fred, S. M., Elsilä, L. V., Sakson, S., Cannarozzo, C., Diniz, C. R. A. F., Seiffert, N., Rubiolo, A., Haapaniemi, H., Meshi, E., ... Castrén, E. (2023). Psychedelics promote plasticity by directly binding to BDNF receptor TrkB. Nature neuroscience, 26(6), 1032-1041. https://doi.org/10.1038/s41593-023-01316-5.