In a new study, researchers examined the role of cholesterol in both Alzheimer’s disease and Type 2 diabetes.
They found a small molecule that may help regulate cholesterol levels in the brain, making it a potential new therapeutic target for Alzheimer’s disease.
The research was conducted by a team at the University of Arizona.
In the last decade, scientists have found increasing evidence linking the underlying causes of Type 2 diabetes and Alzheimer’s disease.
Type 2 diabetes occurs when insulin becomes less efficient at removing glucose from the bloodstream, resulting in high blood sugar that can cause abnormal cholesterol levels.
A similar situation occurs in Alzheimer’s disease, but rather than affecting the body as a whole, the effects are localized in the brain.
In the study, the team tried to develop a way of identifying compounds that would counteract many detrimental changes that contribute to both Alzheimer’s and Type 2 diabetes.
When cholesterol rises, due to insulin resistance or other factors, the body starts a process known as reverse cholesterol transport, during which specific molecules carry excess cholesterol to the liver to be excreted.
Apolipoprotein E (APOE) is one of the proteins involved in reverse cholesterol transport.
APOE is also the strongest risk factor gene for Alzheimer’s disease and related dementia, and an independent risk factor for Type 2 diabetes and heart disease.
Similarly, reduced activity of another cholesterol transporter, ABCA1, correlates with increased risk of heart disease, Type 2 diabetes and Alzheimer’s disease.
Moving cholesterol to where it is needed in the body has positive effects on many physiological processes and can help clear misfolded proteins that accumulate in the brain.
In this study, the team designed a way to identify small molecules that improve the function of ABCA1 in the body while avoiding unwanted effects on the liver.
They honed in on a specific small molecule, CL2-57, due to its ability to stimulate ABCA1 activity with positive effects on liver and plasma triglycerides.
The use of this compound showed improved glucose tolerance and insulin sensitivity, as well as reduced weight gain, among other beneficial effects.
Their future research will seek to improve the properties of the small molecules to increase the levels in the brain.
The long-term goal is to understand which patients suffering from the cognitive and neuropsychiatric symptoms of Alzheimer’s and dementia will benefit from the treatment.
The study is published in ACS Pharmacology and Translational Science. One author of the study is Gregory Thatcher, Ph.D.
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