Uncovering hidden mechanisms in Alzheimer’s disease
“Alzheimer’s is a very complex disease,” observed James Lee, a University of Missouri biological engineering assistant professor, reflecting on the research he is conducting on a form of dementia that has robbed an estimated 26.6 million people worldwide of the spark of mental acuity responsible for their personal identities.
Breakthrough findings from an initial National Institutes of Health research project conducted by Lee and collaborators, Grace Sun, an MU biochemistry professor, and Lee’s former doctoral student, Donghui Zhu, were published in the Journal of Neuroscience last year.
The research team focused on a protein, amyloid-beta peptide, which is present at toxic levels in the brains of those suffering from Alzheimer’s. The researchers looked carefully at how A-beta interacted with the cells in the brain known as astrocytes. These cells, vital to the transmission of neural messages, responded to the toxin by activating a critical enzyme — phospholipase A2 — that negatively effected mitochondria, responsible for energy production. The interaction resulted in increased oxidative stress in cells and led to neuron death.
Each reaction is implicated in the responses of the others, so further research is aimed at understanding cause and effect mechanisms that trigger these responses “Whether A-beta is the cause of the disease or is a result of Alzheimer’s is still a matter of debate — a ‘chicken or the egg’ question,” Lee said.
Every 72 seconds, another American is diagnosed with Alzheimer’s disease. A recent article in the New York Times places the current cost of caring for AD patients at $100 billion a year and goes on to say that by 2050, the number of people in this country suffering from Alzheimer’s may reach 16 million.
Recognizing the importance of the research being conducted by Lee and his associates, the National Institutes of Health awarded Lee significant funding to continue his work. Lee also received an Alzheimer Association new investigator research award, one of only a handful awarded worldwide.
“Astrocytes and their interactions with A-beta and phospholipase A2 have been understudied in relation to Alzheimer’s, but based on my findings, it seems to be important,” said Lee. He is hopeful that his research may unravel information about the disease that will someday lead to effective treatment.