The researchers also found an increase in tumor necrosis factor alpha (TNFα) in MCI brains. TNFα is an inflammatory cytokine or cell signaling protein required for amyloid protein induced neuronal death. Biochemical examination of the autopsy tissue showed that TNFα rather than other cytokines increases the response to BACE1 protein expression. The increased levels of TNFα in MCI and AD patients were not significantly different from each other.
"There is more and more evidence that BACE1 is intricately involved in the development of AD," says the study's lead investigator Yong Shen, PhD, of the Center for Advanced Therapeutic Strategies for Brain Disorders at Roskamp Institute, Sarasota, Florida. "Our previous studies have demonstrated elevated BACE1 enzymatic activity in AD brains and in the cerebrospinal fluid from MCI and AD patients. Our findings here suggest that BACE1 increases early in the course of MCI and is possibly induced by inflammatory molecules like TNFα and that BACE1 enzymatic activity may be important for conversion of MCI to AD. Importantly, we found that the BACE1 activity in tissue from people with MCI was significantly increased by 27%, compared with that from people with no dementia.
"We believe that BACE1 activity precedes the clinical diagnosis of AD and could be an early indicator of neuronal dysfunction or pathology in AD. Moreover, it may be a good therapeutic target for AD, as evidenced by recent promising clinical trials on BACE1 inhibitors," he concludes.
|Contact: Eileen Leahy|
Elsevier Health Sciences