New research could lead to effective preventive treatment for Alzheimer's disease
Due to a large number of baby boomers entering their senior years, the number of Alzheimer’s disease victims is expected to soar. Genetic testing for determining if an individual is a carrier of the ApoE4 protein is currently available; it is s a genetic risk factor associated with a 10-fold higher risk of developing the devastating neurodegenerative disease that rob an individual of his or her dignity and quality of life. However, for years, many individuals with a family history of Alzheimer’s disease have shied away from the test because they are fearful of a positive result. New research has found that these individuals should undergo the test because, those with a positive result could avail themselves of intervention methods that could slow the progression of the disease. The findings were published online on October 21 in the journal Proceedings of the National Academy of Sciences.
Researchers from The Buck Institute for Research on Aging, an independent research association based in Novato, California, have a keen interest in discovering why ApoE4 is associated with such a high risk for Alzheimer’s disease. Although the existence of the protein has been known for two decades, it is currently unknown why it is associated for such a high risk for Alzheimer’s disease.
The investigators note that prior research has been focused on the discovery that ApoE4 appears to affect the clearance of amyloid-beta (A-beta), which is a plaque that builds up in the brains of Alzheimer’s disease victims. However, the investigators were not convinced that this finding offered a complete explanation for the increased risk. They found that ApoE4 was also associated with a significant reduction in SirT1, a protein associated with anti-inflammation, anti-aging, and longevity. They noted that as SirT1 decreases, it affects a certain protein crucial to the storage or loss of memories: the amyloid precursor protein (APP). This molecule is present in neurons and most cells of the body, and at all times this APP is getting cleaved. Cleavage can result in two alternative patterns; thus, APP can go in the direction of memory or forgetting. Individuals with Alzheimer’s disease are on the negative size of this process; they forget rather than retain memories.
The researchers suggest that if SirT1 levels can be maintained, it will prevent these proteins going in the wrong direction. As a result of their discovery, the investigators attempted to identify drugs that might be able to maintain levels of SirT1 in ApoE4 cell cultures. To date, they have successfully identified four drugs that appear to be effective; however, their findings have not yet been tested in humans.
The investigators also conducted experiments in which they successfully reinserted SirT1 proteins back into cells already affected by ApoE4. This process was able to correct the abnormalities present in the cell and return it to a healthy state. This led them to theorize that treatment might be possible even for those already entering the early stages of Alzheimer’s. They noted that, currently, most individuals do not want to know if they have ApoE4 because the knowledge will provide no benefit; however, their study suggests that the knowledge could lead to effective early intervention. They compared it to one knowing that he or she has high blood pressure or elevated cholesterol levels.