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Brain at risk? Researchers are considering whether high homocysteine could help turn a normal brain (bottom) into one with Alzheimer's disease (top).

New Alzheimer's Risk Factor Pinned Down

In the struggle to identify who may be at risk for Alzheimer's disease, scientists have been examining an intriguing link: Alzheimer's and heart disease share some risk factors, such as high cholesterol. Now researchers report that the two diseases share another common sign. Elevated levels of a molecule called homocysteine, already implicated in diseased hearts, also appears to dramatically increase the chance of Alzheimer's.

In well-nourished people, the amino acid homocysteine is broken down by B vitamins and folic acid. But people lacking these key nutrients can have elevated homocysteine levels, and high levels have been associated with heart disease. Because high cholesterol has in some studies been linked to Alzheimer's, some scientists have wondered whether high homocysteine levels may also help trigger the brain disorder.

To find out, Boston University neurologist Sudha Seshadri and her colleagues turned to the Framingham Heart Study, which began following the health of 5209 volunteers in 1948 and has been used extensively in medical studies. In the mid-1970s, the volunteers joined an effort to examine dementia (none had it at the time) and have since undergone regular cognitive function tests. Researchers also collected and stored periodic blood samples from the participants.

Seshadri's group retrieved blood samples dating back as far as 1979 for 1092 members of the dementia study. The scientists measured homocysteine levels and levels of B6 and B12 vitamins; they also searched for variants of a gene called APOE that help predict someone's risk of Alzheimer's. The results were startling: The higher the homocysteine level, the more likely a person was to later develop Alzheimer's. When plasma homocysteine hit a high level--above 14 micromoles per liter of blood--the risk of disease doubled. A 5-micromole increase was linked to a 40% increased risk of disease. The researchers were surprised, they report in the 14 February issue of The New England Journal of Medicine, to find that the newfound risk factor did not depend on someone's vitamin levels or APOE profile.

The strength of the association is powerful, says Joseph Loscalzo, chair of the department of medicine at Boston University Medical Center, who was not involved in the study. But he and others wonder why homocysteine has such an effect. And it is unknown, he adds, whether a person can protect against Alzheimer's by taking vitamins that lower homocysteine levels.

Related links
Framingham Heart Study
Alzheimer's research at Boston University
Alzheimer's research forum
More on homocysteine