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----------------------------------------------------------------------- How Brain Fat Hikes Dementia Risk ----------------------------------------------------------------------- NEW YORK (Reuters) -- Researchers may have moved a step closer to understanding how certain protein molecules in the brain may increase a person's risk of developing Alzheimer's disease. In a report presented this week at the Society for Neuroscience annual meeting in New Orleans, Louisiana, University of Chicago researchers say apolipoproteins that transport cholesterol in the brain differ from those found elsewhere in the body. Several years ago, a natural genetic variant of the fat-transporting apolipoprotein E -- APOE4 -- was linked to an increased Alzheimer's risk. Dr. Mary Jo LaDu, assistant professor of pathology at the University says although the brain is 70% fat, scientists know very little about how fats, or lipids, are metabolized and transported within it. "Because there is no communication between the blood and the brain, we wanted to establish what fat particles are servicing the brain," she says. "We tried to characterize the particles that might be secreted by the particular cells in the brain that manufacture lipid-carrying particles." The researcher notes that the huge amounts of fat and cholesterol are constantly moving around the brain because these compounds are major components of nerve cell membranes, which the nervous system must rearrange as it makes and breaks links from cell to cell. "If there's one organ in your body that needs to be plastic and adaptable, it's your brain," LaDu says. "It's constantly making new synaptic junctions that allow you to form a thought or hold a memory." According to the Chicago pathologist, this means the brain must have a dependable source of cholesterol because it is a vital component of membranes. But the brain also must be able to clear the excess because it is also very toxic to the sensitive nerve cells. This is where astrocytes come in. According to LaDu, these brain cells make lipoproteins as well as nourishing and supporting nerve cells. "Neurons are pretty particular about the environment they live in. They like just enough cholesterol but not too much," LaDu explains. "It's certainly possible that the cholesterol level surrounding a neuron is going to contribute to its viability. And so the ability of astrocytes to secrete particles that are both going to deliver and clear cholesterol to the neurons will certainly determine the general happiness level of the neurons." The researcher and her colleagues analyzed lipoprotein particles found in the cerebrospinal fluid (CSF) and those found in the brain. She says it is those nourishing and supporting functions of lipoprotein particles produced by astrocytes that appear to make them different from those found in the CSF, which bathes the entire nervous system. Among these particles are forms of APOE, including APOE2, APOE3, and APOE4 -- the Alzheimer's risk factor. LaDu says these particles may play a role in clearing the a-beta amyloid proteins that accumulate to form plaques during Alzheimer's disease -- plaques that disrupt neurons. "We think that these lipid particles may also be clearing a-beta amyloid, the primary component of Alzheimer's disease plaques," she says. "And we think a particular form of APOE -- APOE4 -- is not as good at clearing a-beta, as the other naturally occurring forms. We think APOE2 and APOE3 are good at binding and clearing a-beta (amyloid) and APOE4 is not," says LaDu. The researcher sees this as another of the "amyloid hypotheses" linking amyloid plaque deposits with APOE4. This week, Reuters reported findings from Lilly Research Laboratories in Indiana pointing to a link between APOE4 and the development of amyloid plaque fibers. "But this one (the Chicago hypothesis) occurs kind of before the fact," before the development of plaque fibers. Thus, says LaDu, "if you have more APOE2 or APOE3 than APOE4, you can clear things out before they get messy." By Leslie Lang 1997, Reuters Health eLine <http://www.medscape.com/reuters/wed/t102810f.html> ----------------------------------------------------------------------- janet paterson - 50/9 - sinemet/selegiline/prozac - [log in to unmask]