A connection between BDNF and Alzheimer’s disease

Alzheimer's disease is currently the most common cause of dementia. In Alzheimer's disease, brain cells and the synaptic connections between them progressively degenerate, which eventually results in loss of memory, impaired cognitive functions, and other behavioral deficits. The neuropathogenesis of Alzheimer's disease is characterized by the formation of two important protein aggregates, extracellular amyloid beta (Aβ) aggregates and intracellular tau aggregates (Kurbatskaya et al., 2016). Together, Aβ assemblies and tau aggregation cause loss of synapses, neurodegeneration, and cell death. Although extensive studies have been done on Alzheimer's disease and the neural mechanisms underlying Alzheimer's disease progression, no effective treatment has been found for this neurodegenerative disorder. Recent studies have found that brain-derived neurotrophic factor (BDNF) could be a potential target for Alzheimer's disease therapeutic strategies.  

BDNF is a protein made by brain cells that play an important role in synaptic plasticity and the memory processes. The activity of BDNF has been linked to many human diseases including neurodegenerative diseases, such as Alzheimer’s disease. In the article, “Serum pro-BDNF levels correlate with phospho-tau staining in Alzheimer’s disease”, Bharani et al. investigated the relationship between the serum BDNF levels and neuropathogenesis of Alzheimer’s disease. Researchers examined levels of tBDNF, pro-BDNF, and mBDNF in postmortem CSF, serum, and brain tissue. Those measurements were correlated with levels of phospho-tau aggregates and BDNF receptors (TrkB and p75NTR) in the hippocampus. Results indicated that BDNF levels in CSF were lower in the AD group compared to the controls, and lower levels of pro-BDNF in the hippocampus was linked to higher levels of tau aggregates (Bharani et al., 2020). Overall, results demonstrated that levels of BDNF and TrkB receptors are correlated with AD pathology, and AD brains with higher BDNF levels had lower AD pathology and astrogliosis (Bharani et al., 2020). 

Another study that sought to understand the role of BDNF signaling pathways in Alzheimer's disease is a review article called “The role of CREB and BDNF in neurobiology and treatment of Alzheimer's disease” by Amidfar et al. In this study, the researchers investigated the role of CREB-BDNF signaling pathways in AD development. They suggested that extracellular amyloid beta (Aβ) aggregates decrease BDNF expression by decreasing CREB phosphorylation. Together, Aβ aggregates and suppressed BDNF levels cause loss of synapses and memory deficits in AD (Amidfar et al., 2020). Furthermore, increasing the levels of BDNF in the mouse model of Alzheimer's disease, resulted in improved spatial memory and lowered synaptic loss. Therefore, developing a therapeutic strategy based on the targeting of BDNF signaling pathways could be a potential treatment for Alzheimer's disease (Amidfar et al., 2020). 

Overall, a large body of research, including Dr. Bharani’s study and Dr. Amidfar’s article, has provided evidence for a correlation between the reduced BDNF levels and neuropathogenesis of Alzheimer's disease. So far, most of the treatment strategies for AD have either failed or had a temporary effect on AD progression (Amidfar et al., 2020). Therefore, studies like Dr. Bharani’s project are important for understanding the underlying mechanisms of AD and for targeting BDNF as a promising therapeutic strategy for Alzheimer's disease.  

 

References:

 

Amidfar, d. (2020). The role of CREB and BDNF in neurobiology and treatment of Alzheimer’s disease. Life Sciences (1973), 257, 118020–118020. 

 

Bharani, L. (2020). Serum pro-BDNF levels correlate with phospho-tau staining in Alzheimer’s disease. Neurobiology of Aging, 87, 49–59. 

Kurbatskaya, K., Phillips, E., Croft, C., Dentoni, G., Hughes, M., Wade, M., Al-Sarraj, S., Troakes, C., O’Neill, M., Perez-Nievas, B., Hanger, D., & Noble, W. (2016). Upregulation of calpain activity precedes tau phosphorylation and loss of synaptic proteins in Alzheimer’s disease brain. Acta Neuropathologica Communications, 4(1), 34.