Examining the role of cholesterol in both Alzheimer’s disease and Type-2 diabetes, researchers have identified a small molecule that may help regulate cholesterol levels in the brain, making it a potential new therapeutic target for Alzheimer’s disease.
There is no known cure for Alzheimer’s disease and 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 localised in the brain.
“Alzheimer’s and diabetes share many common causes,” said study co-author Gregory Thatcher, Professor at the University of Arizona College of Pharmacy.
“Our goal was to develop a way of identifying compounds that would counteract many detrimental changes that contribute to both Alzheimer’s and Type-2 diabetes,” Thatcher added.
When cholesterol rises, due to insulin resistence or other factors, the body starts a process known as reverse cholestrol 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 cardiovascular disease.
Similarly, reduced activity of another cholesterol transporter, ATP-binding cassette transporter A1 (ABCA1), correlates with increased risk of cardiovascular disease, Type-2 diabetes and Alzheimer’s disease.
Increasing the activity of ABCA1 is expected to positively influence 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 designed a way to identify small molecules that improve the function of ABCA1 in the body while avoiding unwanted effects to the liver. ( IANS )