Age-related cognitive decline has been prevented in fruit flies with Alzheimer's gene mutation by treating them with drugs such as lithium, or by genetic manipulations that reduced nerve-cell signalling.
Researchers, led by Dr.Thomas A. Jongens associate professor of Genetics at the University of Pennsylvania School of Medicine, worked with the familial form of Alzheimer's disease (FAD), an aggressive form of the disease that is caused by mutations in one of the two copies of the presenilin (PS) or amyloid precursor protein (APP) genes.
AdvertisementStudies in animal models have previously shown that the FAD-linked PS mutations lead to less presenilin (psn) protein activity.
"The results from our study suggest a new route to explore for the treatment of familial Alzheimer's disease and possibly the more common sporadic forms of Alzheimer's disease. They also reveal that proper presenilin activity levels are required to maintain normal cognitive capabilities during aging," noted Jongens.
The researchers found that with age, the presenilin mutant - the Alzheimer's fruit fly model-lost the ability to learn and remember and that this age-onset cognitive deficit could be prevented by treating the flies with drugs, or by genetic manipulations that reduce metabotropic glutamate receptor (mGluR) signalling.
MGluR is located on the surface of neurons, including in the hippocampus - a major memory and learning center in the brain.
In addition, treatment of older flies with these same drugs reversed the age-dependent deficits.
"A clear advantage of the drugs used in this study is that one, lithium, is currently FDA approved for other indications and the other class of drugs, the mGluR antagonists, are currently in clinical trials in humans for the treatment of Fragile X syndrome," said a co-author of the study.
"We demonstrate that these treatments, even when begun after the onset of cognitive impairment, can reverse memory deficits. This indicates that there is a window of time during which memory is impaired, but the cellular function can still be rescued with proper treatment, again allowing for the ability to form proper memory. This is a critical finding since in humans Alzheimer's is diagnosed only clinically after the onset of cognitive impairment. So, this finding may indicate that even at the point of early memory impairment, the disease may be reversible," added another co-author.
The study findings are published in this week's issue of the Journal of Neuroscience.