Where are we on the "cognitive end" these days?

Haven't heard anything lately.

More reason for BP to step up here?

https://www.sciencedaily.com/releases/2021/03/210325150226.htm

The paper, "Discovery of Nonlipogenic ABCA1 Inducing Compounds with Potential in Alzheimer's Disease and Type 2 Diabetes," was published in the journal ACS Pharmacology and Translational Science.

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.

"While most people are aware of so-called 'good cholesterol,' and 'bad cholesterol,' associated with risk of heart attack and stroke, these broad concepts are also applicable to a healthy brain," said Dr. Thatcher, who has been working to develop advanced therapeutics for Alzheimer's for more than 20 years. "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."

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, Dr. 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.

In a March 20 paper in the journal EBioMedicine, "Metabolomic analysis of a selective ABCA1 inducer in obesogenic challenge provides a rationale for therapeutic development," Dr. Thatcher's team 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.