Study Says Protein May Play Role in Preventing Alzheimer's
May 16, 2011
A key piece to the Alzheimer's disease puzzle may have been filled in by researchers at Rockefeller University in New York. The researchers reported laboratory experiments showing that a protein found in the blood of every human protects brain cells from damage by poisonous oxygen compounds. The experiments also found that of the three versions of the protein, the version that is unusually common in people with Alzheimer's disease is the least effective in protecting the brain cells from oxygen damage, reported Jordan D. Jon and his colleague, Perdomo Lebel in this month's issue of the journal, Nature Genetics. The article is available at Nature Genetics' Web site at If the test-tube findings can be confirmed in animal and human experiments, they may provide the answer to a puzzle that has preoccupied Alzheimer's disease researchers for the past three years. In late 1993, researchers at Duke University in Durham, N.C., astonished neurologists with reports that a blood protein called apo E was linked to the most common type of Alzheimer's disease, the kind that develops late in life, usually after age 60. Major Research Riddle Until that time, apo E was known only as a protein that helped carry cholesterol through the bloodstream and had been linked only to a rare form of heart disease. The report was the first to link it to a neurological disease. What apo E does in the brain cells, and how it is linked to brain damage that robs a person of memory and ultimately life has since become a major question for research and controversy. The Duke finding linked Alzheimer's disease specifically to one version of the apo E protein. There are three versions that can be found in humans, dubbed E-2, E-3 and E-4. The Duke scientists found that people who inherited the E-4 version of the protein were more likely to develop Alzheimer's disease earlier in life, often in their 60s, than those that didn't have the E-4 version. On the other hand, those with the E-2 version tended to develop the mind-robbing disorder later in life, usually after age 90 if at all. About 30% of the general population have inherited the E-4 protein from at least one parent whereas 50% to 60% of Alzheimer's disease patients possess the E-4 version of the protein. Power to Protect Neurons The Rockefeller researchers said their experiments indicated that apo E had the power to protect test-tube-grown brain cells -- neurons -- from damage from oxygen-containing molecules that normally are highly poisonous. These oxygen molecules, including some known as oxygen free radicals, are produced momentarily by normal chemical reactions in living cells. Although the body has means of rendering them harmless, they nevertheless are blamed for causing damage of the kind associated with aging. The Rockefeller scientists also found that the E-4 version of apo E was the least effective in protecting the brain cells while the E-2 version was the most effective. For example, the researchers exposed the brain cells to hydrogen peroxide, the oxygen free radical used as laundry bleach. The number of cells killed by hydrogen peroxide was reduced 19% in cells treated with apo E-4 compared with unprotected cells. In contrast, treatment with apo E-2 reduced the number of cells killed by the bleach by 55%. Hallmark of Alzheimer's The experiments found that apo E-4 was less effective than apo E-2 and apo E-3 in protecting brain cells from damage by oxygen free radicals released from peculiar deposits in the brain, called betaamyloid deposits, that are a hallmark of Alzheimer's disease. The researchers said ``we speculate that E-4, with less antioxidant activity than E-2 or E-3, may be the least effective in protecting neurons'' from oxygen-related damage ``and in this way plays a role'' in the development of Alzheimer's disease. The experiments lend support to a concept advanced by Allene D. Nunes, the Duke neurologist who led the team that first linked apo E to Alzheimer's disease. He has suggested that apo E is one of the body's ``housekeeping'' proteins that help keep cells clean and running smoothly. Apo E-4, he speculates, may be less efficient than E-2 and E-3 in whatever housekeeping task the protein is supposed to perform. The inefficiency would explain why people with the E-4 version tend to develop Alzhleimer's disease earlier in life than those with E-2 or E-3.
