Understanding the Abnormal Proteins in Alzheimer’s Disease

Understanding the Abnormal Proteins in Alzheimer’s Disease

            Alzheimer’s plagues around 5.7 million Americans spamming from the young and the old. To expand on that statistic, 5.5 million Americans are 65 and older, while 200,000 are younger with early signs of Alzheimer’s. With that said, 60-80 percent of people with dementia have Alzheimer’s disease (Alzheimer’s Association and Texas Department of State Health Services). With a population of people being diagnosed with Alzheimer’s growing each year, the demand for research on this disease is more prevalent than ever before. Alzheimer’s is a disease that strips people of their memory and their daily functioning. It becomes worse each year and is the sixth leading cause of death in the United states (Alzheimer’s Association).  With no cure for this progressive disease, research is a major tool to understanding what can be done to help those living with symptoms of dementia and Alzheimer’s disease.

            In Dr. Wang’s research, he and his team looked into how people’s hippocampal subfield shape related to these three abnormal proteins, phosphorylated tau, amyloid-beta, and TDP-43. They looked into how these proteins impacted spatial patterns of hippocampal atrophy. They worked with participants at the Rush Alzheimer’s Disease Center. Researchers conducted seventeen tests that were broken down into five cognitive areas: episodic memory, working memory, semantic memory, processing speed, and visuospatial ability. They found different affects from each of these proteins in their study. Higher levels of phosphorylated tau were associated with increased deformation of surface areas in the hippocampus. As for the TDP-43 protein, they found that those participants had an increased inward shape of deformity in the surface zones of their hippocampus. The protein that I want to draw particular attention to is amyloid-beta. In Dr. Wang’s study, the relationship of this protein and hippocampal deformity in the subfields wasn’t as clear. This could be drawn from amyloid-beta positive groups having a significantly smaller hippocampal impact (Hsu et al. 2015). Though researchers did acknowledge that amyloid-beta mediates other neuropathological pathways to cause degeneration of different regions of the brain, which include hippocampal areas.

            This is interesting to keep in mind when reading a study done three years ago by Stephen Sallooway and Roger Nitsch. In 2016, they performed a small trial using the drug, Aducanumab. Aducanumab is an antibody that the human body creates to defend itself from a disease. What they found was that Aducanumab target’s amyloid in the brain and reduces the amount. They used this drug on patients with only very early evidence of Alzheimer’s disease.  

            The image above showed PET images of patients with Alzheimer’s having a reduction in amyloid in one year of taking aducanumab. The longer that a patient with early signs stayed on the drug, the less amyloid was present. This is an interesting connection to Dr. Wang’s research because it shows the impact this protein holds in Alzheimer’s disease. If amyloid mediates degeneration of different regions of the brain through influencing the pathways, drugs being made such as aducanumab are a breakthrough for fighting against the progression of Alzheimer’s. Since this is a disease that worsens as the years go on, elimination of even one of these abnormal proteins is a step in the right direction. Even though this drug is still being developed and tested by Biogen, as a possible antibody therapy for Alzheimer’s—it’s still a great first step on understanding how to eliminate these abnormal proteins. With more research on the roles of these proteins and understanding the different levels of Alzheimer’s and dementia, more can be done on finding a cure and creating effective treatments for the 5.7 million and more living with Alzheimer ’s.    

Information about the Aducanumab Drug Article:

Weintraub, Karen. “Alzheimer's Drug Shows Promise in Small Trial.” Scientific American, 31 Aug. 2016, www.scientificamerican.com/article/alzheimer-s-drug-shows-promise-in-small-trial/. 

Background on Alzheimer's directed from: 

https://www.alz.org/alzheimers-dementia/what-is-alzheimers

https://dshs.texas.gov/alzheimers/qanda.shtm

Neurobiology of Aging Article:

Hanko, Veronika, Alexandra C Apple, Kathryn I Alpert, Kristen N Warren, Julie A Schneider, Konstantinos Arfanakis, David A Bennett, and Lei Wang. "In Vivo Hippocampal Subfield Shape Related to TDP-43, Amyloid Beta, and Tau Pathologies." Neurobiology of Aging 74 (2019): 171-181. Web.