Seeking Answers in Alzheimer's Disease

By Suraj Upadhya

Alzheimer’s Disease (AD) is the sixth leading cause of death with more than 5 million cases occurring in the United States. The number of AD cases is projected to soar to 13.8 million by 2050. Thus, AD poses a financial concern to society and an emotional burden on caregivers and families. However, despite the effort to find treatments or a cure to the disease, clinical studies have failed, and AD remains an unmet medical need. Understanding the genetics of AD may advance the discovery of novel therapeutic targets and early diagnostic measures. Moreover, AD is a heterogeneous disease. In AD patients, neuropsychiatric symptoms (NPS) occur frequently, emerging sporadically or persistently with differing severity. This heterogeneity of AD is not well understood, and proper care of AD patients may differ based on severity.

As a junior, I joined the Bass Connections team to understand the genetics underlying NPS, specifically depression and anxiety, in AD. My goal was to identify a way to predict those at greater risk of developing either depression or anxiety. To accomplish this, I created polygenic risk scores, which provide a metric of aggregated genetic risk for developing depression. In doing so, I experienced many of the trials and tribulation that comes with research. I learned new data analysis techniques, with each step forward followed by several new problems to face. Moreover, I realized the importance of a thorough, dynamic analysis plan because despite some struggles, knowing what came next was helpful. However, the next step could be a result of the step prior at times. Thus, my experience exposed that one must be flexible in research. After I received a result, the fun began in trying to interpret the results and provide biological meaning.

With the Student Research Award, I was able to publish my work as we created a PRS that was effective in predicting depression risk among AD patients. This experience brought an understanding as to how others can read words much differently than they were initially intended. I found that when considering reviewer comments, it is still best to stay true to your word and your thoughts. The skill is in finding the right balance. Reviewer comments helped strengthen the paper, which increased understanding among readers, in turn, increasing awareness of the work conducted by the Bass Connections team that showed how impactful our results were. The Bass Student Research Award allowed me to travel throughout the research journey, from proposal to communicating the results. However, research has no end. Therefore, the work I’ve done this past year reinforces my path towards additional answer-seeking, as one question always leads to another.