Researchers find link between protein, Alzheimer's
While cautioning that more research is needed, Framingham Heart Study investigators have found an association between levels of a protein that regulates weight and appetite and the onset of Alzheimer's and dementia.
The protein, leptin, is produced by both fat cells and muscles before circulating in the blood. But while the molecule is small and could be produced to give to humans, heart study investigators say it's too soon to tell if treatment levels or pills could ward off brain degradation.
"Many of these things are promising in animals and then when you take it to humans it doesn't seem very helpful in terms of treatment," said Dr. Sudha Seshadri of Boston University's medical school. "We need to make sure this is real and determine what the significance is."
The investigators' research appears today in the Journal of the American Medical Association. It builds off an existing association, that those with Alzheimer's or at greater risk for the disease have smaller hippocampi, a portion of the brain tied to long-term memory.
But since the hippocampus is hard to access and measure, scientists typically look at the temporal horn, another part of the brain that holds cerebral fluid. Small hippocampi mean big horns, and vice versa.
While leptin has a strong tie to feelings of fullness, previous animal research has shown that the protein also helps memory-forming cells in the hippocampus. So heart study investigators followed participating dementia-free Framingham residents for a dozen years, measuring their temporal horns and leptin levels.
The results show high leptin levels associated with small temporal horns, a good outcome, and low levels associated with big horns, a bad one. Put another way, those with low levels are suspected of having a 25 percent chance of developing Alzheimer's and those with high levels a 6 percent chance.
In addition to its suspected benefits to memory-forming cells, researchers believe that leptin helps stop the blocks and tangles associated with Alzheimer's.
Seshadri said her team still needs to look at other populations and the role genes may play, with scientists unsure about all the factors that cause varying leptin levels and wary of targeting one molecule at the risk of throwing other bodily functions off balance.
If leptin does prove a reliable benchmark, it could be added to the list of risk factors for Alzheimer's and dementia, with heart study researchers also looking at other possibly connected substances.
The National Institute on Aging says the causes of Alzheimer's are not yet fully understood, with genetic, environmental and lifestyle factors all likely contributors.
During their study, Seshadri and other researchers found high leptin levels in participants who were slim, healthy and ate a good diet, but still higher levels in those who were obese.
Under the "leptin paradox," researchers suspect that obese people have resistance to leptin and its feelings of satiety but that their bodies keep producing ever more molecules in an attempt to compensate.
"This is not, unfortunately, a simple message," Seshadri said.
Michael Morton can be reached at firstname.lastname@example.org or 508-626-4338.