Many lines of evidence suggest that beta-amyloid peptides cause neuronal damage and affect fundamental memory processes early in the course of Alzheimer’s disease (AD). Two membrane-associated enzymes, namely β-secretase (BACE1) and γ-secretase are responsible for β-amyloid production. As a result, inhibitors for either enzyme have been developed and are being tested in clinical trials. Whether one could lead a healthy life without these enzyme activities is a critical question. These enzymes are important for a myriad of functions in the brain and the body, and so total inhibition of these enzymes may not be the ideal way to target β-amyloid production. Therefore, there is an urgent need to fully understand the normal biological functions of these enzymes, and also to determine whether the cellular and molecular mechanisms involved in β-amyloid production in neurons can be utilized to reduce amyloid burden in the brain, while sparing the other normal neuronal functions of these enzymes.
More recently, we turned our focus on the characterization of late-onset AD risk factors. In particular, we are investigating BIN1, the most significant late-onset AD susceptibility gene identified by GWAS efforts. Our initial manuscripts on BIN1, which describes novel and interesting information on oligodendrocyte expression and white matter localization of BIN1 in rodent and the human brain were recently published.
Ongoing research projects
- BIN1 as a LOAD risk factor
- BACE1 trafficking in neurons
- The role of peripheral amylin in AD pathogenesis
- RNA methylation in AD pathogenesis