Alzheimer's risk factor explained

NEW YORK, Mar 02 (Reuters Health) -- Alzheimer's disease has been the focus of intense research for decades. A new study published in the Proceedings of the National Academy of Sciences may help unravel the mystery of why the presence of a particular protein in the brain leads to the dementia and degeneration associated with this dreaded disease.

Dr. David M. Holtzman of the Washington University School of Medicine in St. Louis, Missouri, together with colleagues there and at the Lilly Research Laboratories in Indianapolis, Indiana, studied mice to explore how apolipoprotein E (apoE) influences amyloid-beta plaque-forming deposits in the brain.

The accumulation of this amyloid protein in the brains of Alzheimer's patients is believed responsible for the damage done to brain nerve cells, Holtzman told Reuters Health.

"In this study, we show that an interaction between apoE and amyloid-beta is critical not only for the build-up of amyloid-beta, but also for an important part of its toxicity in the brains of living animals," he said.

Study co-author, Dr. Steven M. Paul of Lilly Research Laboratories, explained to Reuters Health that the apoE gene is actually "a risk factor gene. If you have two copies of the E4-variant, you have about a 10-fold greater risk of getting Alzheimer's disease." He added that "about half the people with two copies will get the disease by age 65 and about 80% will get it by age 85." In contrast, the presence of the apoE2 variant is protective and reduces the risk of Alzheimer's.

Interestingly, about 10% of people with two copies of the apoE4 gene will never get the disease and Paul speculates that another factor may need to be superimposed on this genetic background to allow the disease to occur.

According to Holtzman,

"the apoE4 variant is much worse (than other human variants) in causing the toxicity" because it seems to encourage more amyloid deposition and the formation of nerve tangles and plaques in areas of the brain that function in learning and memory.

Thus, Holtzman said,

"apoE4 appears to be a critical element" in producing the kinds of tissue changes that ultimately contribute to the impairments characteristic of Alzheimer's.

Studies such as these

"indicate that modification of human apoE levels or interactions with amyloid-beta, will modify Alzheimer's disease," he said, which may open the way for innovative strategies to treat or perhaps prevent the disease.

Paul concurs.

"If we could find a way to reduce apoE expression, since we know what cells make it in the brain, we think we could come up with a drug that might prevent plaque deposition," he said.

Holtzman and Paul both subscribe to the prevailing amyloid deposition cascade theory of Alzheimer's disease development and believe that drugs could conceivably "prevent and certainly reverse Alzheimer's disease," Paul added.

He cautions, however, that such a medication is likely some years away from the market but that the current study is an important step "in solving the genetic riddle" of Alzheimer's.