The Role of BDNF in Alzheimer's Disease

    Infamous for being the 6th leading cause of death in the United States, Alzheimer’s Disease is a degenerative disease that progressively destroys an individual's memory, to the extent in which it interferes with one’s day-to-day life. Though one can be clinically diagnosed with Alzheimer’s Disease using the DSM5, a definitive diagnosis comes through post-mortem neuropathological analysis. Many drugs have tried to treat this debilitating disease and have failed to make an impact, proving the importance of finding new ways to not only treat but diagnose Alzheimer’s Disease. 

    In the article “Serum pro-BDNF levels correlate with phosphor-tau staining in Alzheimer’s disease”, Krisha Bharani and colleagues sought to understand the difference and the relationship between total BDNF(tBDNF), pro-BDNF, and mature BDNF (mBDNF) in postmortem CSF, serum, and brain samples between AD and healthy controls. They also wanted to understand the relationship between BDNF levels and the density of amyloid-B, pTau, BDNF receptors and neuroinflammation in the hippocampus to further investigate BDNF’s role in AD pathology. Upon their research, they discovered that BDNF in CSF was seen to be at a lower ratio in AD patients in comparison to the control group. They also found that higher serum pro-BDNF levels were associated with lower hippocampal pro-BDNF levels as well as higher hippocampal pTau accumulation. It is also important to note that they discovered that AD cases with lower astrogliosis had lower AD pathology and higher BDNF levels. 

    This research may be one of the first to investigate the relationship between CSF BDNF levels and the levels seen in brain tissue and serum, and were unique in using post-mortem samples. They are not, however, the only lab to delve deeper into this idea. Sudha Seshadri and colleagues, from Boston University, conducted a study in which they wanted to understand whether blood levels of BDNF could influence the risk of Alzheimer’s Disease. They gathered blood samples from about 2,000 individuals over the age of 60 and measured each one’s BDNF levels. What made this research particularly special was the fact that the researchers had followed their participants over the course of a decade to determine whether any of the them would go on to develop Alzheimer’s disease. After a decade, 117 of their subjects had developed Alzheimer’s. They then assessed if there was any correlations between their BDNF levels and their development of Alzheimer’s and found that there was, in fact, a correlation. They concluded that, though the application of their research was limited to men and women over the age of 80, higher serum BDNF levels may protect against the future development of Alzheimer’s Disease. 

    Both research studies highlight the clinical applications of this field of research which can stretch from earlier diagnoses to even better treatment. They both provide evidence of how BDNF could one day be used as a biomarker for the risk of developing Alzheimer’s Disease, while also proving as a target for treatments. While this is only the start, this research could lead to substantial advancements towards a cure for Alzheimer’s Disease. 

References: 

Bharani KL, Ledreux A, Gilmore A, Carroll SL, Granholm AC. Serum pro-BDNF levels correlate with phospho-tau staining in Alzheimer's disease. Neurobiol Aging. 2020 Mar;87:49-59. doi: 10.1016/j.neurobiolaging.2019.11.010. Epub 2019 Nov 22. PMID: 31882186.

Weinstein, Galit & Seshadri, Sudha. (2014). Serum Brain-Derived Neurotrophic Factor as a Predictor of Incident Dementia Reply. JAMA neurology. 71. 653-4. 10.1001/jamaneurol.2014.215.