Leptin and Alzheimer's Disease

Contributed by: Michael Rafii, M.D., Ph.D - Director of the Memory Disorders Clinic at the University of California, San Diego. ______________________________________

High levels of the energy-regulating hormone leptin were associated with lower rates of Alzheimer's disease in a study appearing in The Journal of the American Medical Association. If confirmed, researchers say the findings could have important implications in the search for effective therapies to prevent and treat the disease.

Discovered in the mid-1990s, leptin is produced by fat cells and is believed to be critical for regulating hunger and weight. But there is growing evidence suggesting a role for the hormone in brain development and memory.

Leptin has been shown to reduce concentrations of Beta-amyloid, the major component of the deposits, or plaques, that occur in the brains of people with Alzheimer's disease.

In the new study, elderly people were followed for up to 15 years after blood leptin concentrations were measured. Over 12 years of follow-up, people with the lowest leptin levels were roughly four times more likely to develop Alzheimer's disease than people with the highest levels.

The study initially included 785 elderly people taking part in the ongoing Framingham Heart Study, which began recruiting patients in 1948. Blood leptin levels were measured between 1990 and 1994. Around eight years later, 198 of the participants who had not developed dementia underwent brain imaging with MRIs to assess brain aging. Those with the highest leptin levels at the beginning of the study had healthier brains with less evidence of aging. Higher early leptin concentrations were associated with lower rates of dementia years later. This association was seen even after they adjusted for the impact of midlife abdominal obesity, which has recently been identified as an early risk factor for Alzheimer's disease.

Future studies will be needed to understand the role of Leptin in AD, and whether leptin replacement could be a therapeutic approach.

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