The Effect of Tau Levels on Alzheimer’s Disease Patients and Tau Immunotherapy

            Alzheimer’s disease (AD), a form of dementia, is a very prominent disease with no known cure. In order to devise an effective treatment several different causes of Alzheimer’s have been analyzed. The tau protein and accumulation of tau as well as BDNF levels are the main causes that will be focused on. The process to find a treatment is very long, the treatment is first devised and then go through clinical trials to analyze their effectiveness. One specific treatment that will be talked about is tau immunotherapy which seems to be a promising treatment for AD patients in the future. 

In the article, “Serum pro-BNDF levels correlate with phospho-tau staining in Alzheimer’s disease” Krishna Bharani and colleagues studied the impact of brain derived neurotrophic factor (BDNF) on the progression of Alzheimer’s disease. The two types of BDNFs focused on were pro-BDNF (premature form) and mBDNF (mature form). Neuron death is likely caused by the high affinity binding of pro-BDNF to the p75 NTR receptor and neuron survival is influenced by high affinity mBDNFs bound to TrkB receptor. BDNF is interesting to study because it is able to cross the blood brain barrier. Cerebrospinal fluid (CSF) levels were measured and low levels of BDNF are found to be correlated with a higher risk of developing AD. BDNF levels were measured in cortical regions as well and were negatively correlated with Amylo-Glo staining in the HIP. This means that lower levels of BDNF in cortical brain regions could interfere with hippocampal amyloid accumulation. Bharani talked about BDNF levels being affected by many factors such as aging, stress, exercise, addiction and obesity. Higher p Tau staining was found to be correlated with less TrkB receptors in the hippocampus. It was also found that high pro BDNF levels were associated with more hippocampus tau staining. Bharani talked about BDNF levels and how they could be correlated with tau levels in the brain, both of which could be used as targets for possible AD treatment.

 

In the article, “Tau-targeting therapies for Alzheimer disease” Congdon and Sigurdsson analyzed different ways to effectively treat Alzheimer’s disease. It is commonly found that tau protein and amyloid beta peptide are some of the main components found in tangles and plaques that build up in the brain and lead to AD. Tau at typical levels provides stability to microtubules and regulates cellular signaling within the cell. In many disease including AD, the normal function of tau is disrupted due to abnormal levels of tau in the brain. Tau levels are recorded from samples of CSF. Tau levels are found to be higher in AD patients but as the disease progresses the levels decrease. This could be due to the tau clumping together and being recognized as less tau than what is actually present. This specific article talks about the many directions that treatment for AD including targeting protein modifiers of tau, preventing expression or reducing expression of tau, inhibiting aggregators of tau and stabilizing microtubules. Results from a clinical trial found that immunotherapy targeting anti-A beta antibodies actually reduced phospho-tau levels in the CSF of patients with AD. The shift of AD treatment could be more effective when targeting tau proteins through immunotherapy.

            

            Overall, both Bharani and Congdon and Sigurdsson are making strides in AD research and treatment. The correlation between BDNF levels and tau levels has helped researchers better understand how AD patients will respond to certain treatments. It has also allowed for the creation and execution of new treatments. The tau immunotherapy treatment sounds promising and hopefully will work to better regulate tau levels in the CSF and in the brain. In conclusion, the work that was performed in these two articles is very important in the process to devise new treatments along the path to finding a cure for AD.

Works Cited:

 

Bharani, K. L., Ledreux, A., Gilmore, A., Carroll, S. L., & Granholm, A. C. (2020). Serum pro-BDNF levels correlate with phospho-tau staining in Alzheimer's disease. Neurobiology of aging, 87, 49–59. https://doi.org/10.1016/j.neurobiolaging.2019.11.010

 

Congdon, E. E., & Sigurdsson, E. M. (2018). Tau-targeting therapies for Alzheimer disease. Nature reviews. Neurology, 14(7), 399–415. https://doi.org/10.1038/s41582-018-0013-z