For more than 100 years, the amyloid precursor protein has been the suspected culprit of Alzheimer's disease. As such, the protein has been extensively studied; however, its distribution within and on neurons has remained unclear.
Mastermind or accomplice?
Now, in their quest to fight Alzheimer's, a team of neuroscientists has sought to figure out if the amyloid precursor protein is the mastermind behind the devastating disease or if it is just an accomplice.
Scientists know a lot about how this protein turns into amyloid plaques. However, they have very little information about its native function in neurons.
And there is even more reason to believe the amyloid protein might not be the culprit its been made out to be. For instance, in the case of sporadic Alzheimer's disease, the highest genetic risk factor is a protein that is involved in cholesterol transportation. There is also the fact that clinical trials designed to address the disease by minimizing amyloid plaque formation have failed.
So the researchers decided to tackle this Alzheimer's disease mystery by devising a multi-functional reporter for amyloid precursor protein. For the study, the scientists genetically disrupted the interaction between cholesterol and amyloid precursor protein.
Through this approach, they were surprised to discover that this manipulation not only disrupted the trafficking of the amyloid precursor protein but also messed up cholesterol distribution at the neuronal surface.
An association with cholesterol
"Our study is intriguing because we noticed a peculiar association between amyloid precursor protein and cholesterol that resides in the cell membrane of synapses, which are points of contact among neurons and the biological basis for learning and memory," said Zhang, Ph.D., senior author, investigator at the FAU Brain Institute, and assistant research professor in FAU's Schmidt College of Medicine.
"Amyloid precursor protein may just be one of the many accomplices partially contributing to cholesterol deficiency. Strangely, the heart and brain seem to meet again in the fight against bad cholesterol."
Since cholesterol has a broad involvement in almost all aspects of neurons' life, Zhang and his team have proposed a new theory about the amyloid precursor protein connection in Alzheimer's disease.
"Although still in early stages, this cutting-edge research by Dr. Zhang and his collaborators at Vanderbilt University may have implications for the millions of people at risk for or suffering with Alzheimer's disease," said Randy D. Blakely, Ph.D., executive director of the FAU Brain Institute and a professor of biomedical science in FAU's Schmidt College of Medicine.
"The number of people in Florida alone who are age 65 and older with Alzheimer's disease is expected to increase 41.2 percent by 2025 to a projected 720,000, highlighting the urgency of finding a medical breakthrough."
The study is published in the journal Neurobiology of Disease.