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Does Adiponectin Cause Or Prevent Alzheimer's Dementia?

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Historically, doctors have viewed fat cells as the three-toed sloths of human cell biology. They have been characterized as dumb, inert warehouses of fat. However, over the last 15 years there has been an explosion of data showing that fat cells, or what physiologists call adipocytes, are as active, complicated and communicative as any other cells in the body. Fat is potentially a very dangerous substance in the body and, over time, adipocytes have evolved to help manage its safe storage, distribution and metabolism. To coordinate the use of energy around the body, adipocytes secrete a number of hormones, referred to as adipocytokines. These hormones inform other cells about the energy status of the body and help them burn fats and carbohydrates in a safe and effective manner. One such hormone produced and secreted by adipocytes is adiponectin.

Adiponectin was discovered in 1995, and its functions are not yet entirely known. What is known is that it is produced only in fat cells, and it appears to help insulin and other adipocytokines control fat and glucose metabolism in the human body. By every indication, the activity of adiponectin helps to prevent adverse conditions such as diabetes, cardiovascular disease, obesity, inflammation and what has come to be known as Metabolic Syndrome. Metabolic Syndrome, sometimes referred to as pre-diabetes, is known to be a risk factor not only for diabetes but also for cardiovascular disease and Alzheimer's Dementia. One curious fact about adiponectin is that despite its being produced by adipocytes, or fat cells, individuals who are obese tend to have low levels of adiponectin. This is in contrast with the important adipocytokine, leptin, which tends to be high in the blood of obese individuals.

Adiponectin is now in the news as possibly having a role in the development of Alzheimer's Dementia. However, given the fact that adiponectin tends to reverse conditions that are known to be risk factors for Alzheimer's Dementia, these recent reports about adiponectin are surprising. In a study recently performed by Dr. Ernst Schaefer, a professor of medicine and nutrition at Tufts University, blood samples obtained in the famous Framingham Heart Study were evaluated for the levels of adiponectin they contained. It was found that a disproportionately large percentage of women that went on to develop Alzheimer's or other dementias had high levels of adiponectin in their blood. Similar results were found for men, but the numbers of men evaluated in the study was not sufficient to allow statistical certainty about those results. Dr. Schaefer was understandably surprised to find that women with high levels of the hormone had an increased risk of dementia. However, his finding of high levels of adiponectin in individuals with dementia was not the first. A Japanese study published earlier this year similarly found that levels of adiponectin, both in the blood and in the fluid around the brain, cerebrospinal fluid, were higher in those diagnosed with Alzheimer's Dementia than in normal control subjects.

Those unexpected findings prompt the question: Does adiponectin cause or prevent Alzheimer's Dementia? However, the answer is likely to be complicated. Part of this seeming paradox may lie in the fact that the body can become resistant to effects of some of its own hormones. This phenomenon is evident in Metabolic Syndrome, wherein the body becomes resistant to many of the effects of insulin. In individuals with Metabolic Syndrome who are still able to produce insulin, it is quite common to see high blood levels of insulin. Because the body is resistant to the insulin, blood sugar levels tend to remain high in those individuals despite the raised levels of the insulin that would otherwise normalize those levels.

As with insulin, the body can also become resistant to the adipocytokine leptin. Ordinarily, leptin serves to reduce appetite, but in obese individuals with high leptin levels, this effect of leptin is lost due to resistance. Recent studies have begun to show that the body can also become resistant to adiponectin. Interestingly, in one study of mice, animals found to be resistant to adiponectin had high levels of adiponectin in their blood, as was observed in humans prone to developing Alzheimer's Dementia. Thus, it might very well be the case that adequate adiponectin activity may help reduce the risk of developing Alzheimer's. However, resistance to the hormone may prevent the body from benefitting from the effects of adiponectin. Further research is needed to resolve this new puzzle.

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