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How a decrease in cholesterol levels in nerve cells may disrupt nerve cell communication in Alzheimer’s disease?
Qi Zhang, Ph.D.
Florida Atlantic University
Boca Raton, FL - United States
Background
One of the hallmarks of Alzheimer’s disease is the accumulation of high levels of beta-amyloid protein fragments into plaques in the brain. Beta-amyloid is formed from its parent protein, amyloid precursor protein (APP). Several studies have focused on how APP is cut by specific proteins (called enzymes) inside nerve cells to form beta-amyloid. However, APP may have other functions inside nerve cells.
Dr. Qi Zhang and colleagues have added a fluorescent molecule to APP to visualize its movement and distribution within nerve cells. They have found APP directly interacts with cholesterol—a key component of nerve cells. Disrupting this interaction damages nerve cells. This damage is done by decreasing cholesterol levels in special structures called synapses that nerve cells use to communicate with each other. Synapse integrity is critical for cognitive function.
Research Plan
Dr. Zhang’s team will use new methods using microscopes to more specifically study how APP disrupts cholesterol inside synapses, and how this can harm nerve cells. First, the researchers will measure cholesterol levels and APP distribution in nerve cells growing in laboratory dishes. Then, Dr. Zhang will use drugs and genetic tools to manipulate APP amounts in the nerve cells and then study how this impacts cholesterol levels in nerve cells. In addition, Dr. Zhang will study how cholesterol levels in synapses are impacted by variations in APP found in people with Alzheimer’s disease. Furthermore, the researchers will assess cholesterol levels in nerve cells containing APP that has been cut by different enzymes.
Dr. Zhang’s team will investigate how these manipulations may change synapse cholesterol levels, which could potentially harm nerve cell communication and damage the nerve cells.
Impact
This study may shed light on how a decrease in cholesterol levels in nerve cells could impact nerve cell communication and nerve cell damage in Alzheimer’s disease. If successful, the study results could also provide new tools for future research in Alzheimer’s disease.
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