A faulty molecule, identified in the brain of patients suffering from mild cognitive impairment (MCI) could be responsible for the progression of MCI to Alzheimer's disease (AD) dementia, according to a recent study published in the journal of Neurobiology of Aging.
Researchers at Mount Sinai School of Medicine have indicated that the onset of (AD) dementia may be delayed by eliminating plaque causing beta-amyloid peptides in the brain.
An estimated 4.5 million Americans have Alzheimer's disease and presently there are no known cures or effective preventive strategies.
'Alzheimer's Disease is a growing health concern that affects millions of people, 'says Giulio Maria Pasinetti, M.D., Ph.D., Professor of Psychiatry and Neuroscience, Director of the Neuroinflammation Research Center at Mount Sinai School of Medicine and lead author of the study. 'We hope our research provides direction for preventative treatments to delay the onset of AD dementia by eliminating amyloid plaque-causing peptides in the brain.'
People with AD exhibit elevated levels of beta-amyloid peptides that cause plaque buildup in the brain (the main characteristic of AD). In the earliest stages of Alzheimer's, beta-amyloid peptides are on the rise, especially in the two connected brain regions critical for memory functions-- the hippocampus and entorhinal cortex.
In this study, Dr. Pasinetti and colleagues at Mount Sinai School of Medicine in New York suggests one reason for that early increase of beta-amyloid peptides: an enzyme that breaks down beta-amyloid peptides, also referred to as an insulin-degrading enzyme (IDE), is not active in the brain in the cases at high-risk for developing AD. To assess possible changes in IDE during MCI, the investigators measured protein levels and enzymatic activity in postmortem brain tissue from 46 elderly subjects.
A loss of IDE activity has been previously shown to occur in severe AD dementia, and the current results raise the possibility that a deficit in degradation of amyloid peptides from IDE could raise levels of toxic beta-amyloid peptides even before AD dementia is diagnosed. If these results are confirmed, Mount Sinai researchers suggest that boosting IDE activity pharmacologically may reverse beta-amyloid peptide accumulation. This new finding may provide a pharmacological therapeutic angle to preventing AD dementia.
Dr. Pasinetti and colleagues also measured levels of beta-amyloid peptides in the entorhinal cortex and found that the amount of beta-amyloid was inversely correlated with IDE activity they measured in the hippocampus. These results support the idea that alterations in IDE might be causally related to beta-amyloid peptides accumulation, starting in the earliest stages of AD.