Scientists have known for more than a decade that individuals with a certain gene are at higher risk for developing Alzheimer's disease. Now a new study helps explain why this is so.
The research, led by scientists at the Oklahoma Medical Research Foundation (OMRF), has uncovered a molecular mechanism that links the susceptibility gene to the process of Alzheimer's disease onset. The findings appear in the April 11 issue of The Journal of Neuroscience and may lead to new pathways for development of Alzheimer's therapeutics.
Approximately 15 percent of the population carries a gene that causes their bodies to produce a lipoproteina combination of fat and protein that transports lipids (fats) in the bloodknown as apolipoprotein (Apo) E4. Studies have found that those who inherit the E4 gene from one parent are three times more likely than average to develop Alzheimer's, while those who get the gene from both parents have a tenfold risk of developing the disease.
In the new study, OMRF's Jordan J.N. Tang, Ph.D., and his colleagues discovered that ApoE4 (along with other apolipoproteins) attaches itself to a particular receptor on the surface of brain cells. That receptor, in turn, adheres to a protein known as amyloid precursor protein. The brain cells then transport the entire protein mass inside.
Once inside, cutting enzymescalled proteasesattack the amyloid precursor protein. These cuts create protein fragments that, when present in the brain for long periods of time, are believed to cause the cell death, memory loss and neurological dysfunction characteristic of Alzheimer's.
Although researchers have known for more than a decade that ApoE4 was involvedsomehowin development of Alzheimer's, Tang's new study is the first to connect the process of protein fragment formation to ApoE4.
While roughly 1 in 7 people carry the E4 gene, the remainder of the population carry only two variationsknown as E2 and E3of
Contact: Shari Hawkins
Oklahoma Medical Research Foundation