Lih-Fen Lue, Ph.D.
Sun Health Research Institute
Sun City, Arizona

2008 Investigator-Initiated Research Grant

People at risk of Alzheimer's disease often develop a preliminary condition called mild cognitive impairment (MCI). This condition involves noticeable cognitive loss that is not serious enough to interfere with daily life. Because MCI often precedes Alzheimer's, people with the condition can receive great benefit from treatments aimed at slowing or reversing cognitive loss.

However, MCI appears in many different forms, and not all people with MCI have the same risk of developing Alzheimer's disease. Alzheimer risk is particularly high among people with amnestic MCI. Yet even among these individuals, the conversion rate to Alzheimer's is only 10 to 30 percent. To better pinpoint which individuals with amnestic MCI have the greatest risk of developing Alzheimer's, researchers need to better characterize the biological features that underlie this risk.

Lih-Fen Lue, Ph.D., and colleagues have found that a protein called "soluble receptor for advanced glycation endoproducts" (sRAGE) may play a significant role in dementia progression. This protein interacts with cells of the immune system and has been shown to prevent brain inflammation characteristic in Alzheimer's disease. Dr. Lue's team found that people with amnestic MCI and early Alzheimer’s suffer considerable reductions in sRAGE levels. The researchers hypothesize that this sRAGE deficiency puts people with amnestic MCI at greater risk of inflammation and Alzheimer's.

Dr. Lue and colleagues propose to test their sRAGE hypothesis. They will study a large group of participants with amnestic MCI, mild Alzheimer's or normal cognition over a three-year period. The researchers will statistically analyze reductions in sRAGE levels for all three groups and determine whether these reductions played a role in the worsening of dementia. Dr. Lue's team will also test whether certain immune system cells are responsible for regulating levels of sRAGE in the body.

The results of this study could shed new light on biological mechanisms underlying Alzheimer progression and Alzheimer-related brain inflammation. Such knowledge could lead to novel methods for preventing Alzheimer's or treating the disease in its earliest stages.