Research report: Double whammy for Alzheimer’s disease

By Lynne Friedmann

A study reports that muscle problems in patients taking statins were related to the strength or potency of the cholesterol-lowering drugs.

UC San Diego Medicine researchers teamed up with California-based AdverseEvents, Inc., using the company’s software platform, to conduct a detailed examination of statin side-effect data from the FDA’s Adverse Event Reporting System (AERS). The study analyzed muscle-related adverse events linked to each of the major statin drugs in a total of 147,789 AERS reports gathered over a six-year period.

Looking at the most commonly used statins – both brand names and generic forms — rosuvastatin, the strongest statin, had the highest rates of reported problems. This was a surprise. Experts believed rosuvastatin possessed superior safety because it is less fat soluble and assumed not to penetrate into muscle cells as much as other statins.

The study points to the importance of post-marketed studies utilizing AERS data to understand the lasting side effect risks of widely used medications in disparate populations. Statins, prescribed to lower cholesterol and reduce the risk of cardiovascular disease, are among the most widely taken prescription medications in the world, with over 30 million users in the United States alone.

The underlying causes of Alzheimer’s disease are not fully understood, but evidence points to the accumulation of B-amyloid, a protein toxic to nerve cells. B-amyloid is formed by the activity of several enzymes, including BACE1 found in elevated levels in most Alzheimer’s patients.

Sanford-Burnham Medical Research Institute scientists have found that BACE1 does more than just help produce B-amyloid — it also regulates another cellular process that contributes to memory loss.

In a study to better understand how the enzyme plays a role in memory loss, researchers used a mouse model that produces human BACE1. If BACE1 only acted to produce B-amyloid, there should be no effect on memory in the study mice. Instead, the enzyme was shown to impair learning and memory, indicating a secondary function at work.

Thus, inhibiting BACE1’s enzymatic activi- ty as a means to prevent or treat Alzheimer’s disease wouldn’t be enough—cells must be prevented from making BACE1 at all. But that also means a therapy that blocks BACE1 expression in the brain could potentially benefit patients with normal aging-related memory loss unrelated to Alzheimer’s disease.

Water has been studied more extensively than any other liquid yet its microscopic properties remain poorly understood. Researchers at UC San Diego and Emory University have uncovered fundamental details about the hexamer structures that make up the tiniest droplets of water. A hexamer is considered the smallest drop of water because it consists of the smallest three-dimensional cluster in which the oxygen atoms of the molecules do not lie on the same plane.

This findings lead to a better understanding of the structure and dynamics of water in its liquid state, which plays a central role in many phenomena of relevance to different areas of science, including physics, chemistry, biology, geology, and climate research. For example, the hydration structure around proteins affects their stability and function, water in the active sites of enzymes affects their catalytic power, and the behavior of water adsorbed on atmospheric particles drives the formation of clouds.