Ldl cholesterol could possibly be key to new Alzheimer’s, diabetes therapies : The Tribune India



In studying the role of cholesterol in both Alzheimer’s disease and type 2 diabetes, researchers identified a small molecule that may help regulate cholesterol levels in the brain, making it a potential new therapeutic target for Alzheimer’s disease makes.

There is no known cure for Alzheimer’s disease, and over the past decade, scientists have found increasing evidence linking the underlying causes of type 2 diabetes and Alzheimer’s disease.

Type 2 diabetes occurs when insulin removes glucose from the bloodstream less efficiently, resulting in high blood sugar that can lead to abnormal cholesterol levels.

A similar situation occurs with Alzheimer’s disease, but instead of affecting the entire body, the effects are localized in the brain.

“Alzheimer’s and diabetes have many common causes,” said study co-author Gregory Thatcher, a professor in the University of Arizona College of Pharmacy.

“Our goal was to find a way to identify compounds that counteract many of the harmful changes that contribute to both Alzheimer’s and type 2 diabetes,” added Thatcher.

When cholesterol levels rise due to insulin resistance or other factors, the body starts a process known as reverse cholestrol transport, in which certain molecules move excess cholesterol into the liver for excretion.

Apolipoprotein E (APOE) is one of the proteins involved in the reverse transport of cholesterol.

APOE is also the strongest risk factor gene for Alzheimer’s disease and related dementia, as well as an independent risk factor for type 2 diabetes and cardiovascular disease.

Similarly, decreased activity of another cholesterol transporter, the ATP-binding cassette transporter A1 (ABCA1), correlates with an increased risk of cardiovascular disease, type 2 diabetes and Alzheimer’s disease.

Increasing the activity of ABCA1 is expected to positively affect insulin signaling and reduce inflammation in the brain, making it a potential therapy for both type 2 diabetes and Alzheimer’s disease.

In this study, published in the journal ACS Pharmacology and Translational Science, Thatcher and the research team found a way to identify small molecules that improve the way ABCA1 works in the body while avoiding undesirable effects on the liver.