Alzheimer's Roots

New study zeroes in on the genetic roots of Alzheimer's

Scientists have known for more than a decade that individuals with a certain gene are at higher risk for developing Alzheimer’s disease.

Now 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 lipoprotein—a combination of fat and protein that transports lipids (fats) in the blood—known 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.

The new study 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 enzymes—called proteases—attack 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 involved—somehow—in development of Alzheimer’s, Tang’s new study is the first to connect the process of protein fragment formation to ApoE4.

Alzheimer’s disease is a neurological disorder characterized by slow, progressive memory loss due to the gradual death of brain cells. According to the Alzheimer’s Association, the disease affects more than 5 million Americans, including nearly half the population over the age of 85.
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