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Researchers Using MS, Other Proteomics Technology Show Link Between Heart Failure and Alzheimer's

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This story originally ran on Nov. 16.

Using mass spectrometry and electrophetic technologies, a team of researches reported evidence showing a link between Alzheimer's disease and chronic heart failure this weekend at the American Heart Association's annual Scientific Sessions in Orlando, Fla.

At the conference, the researchers from the US, Canada, and Italy presented evidence identifying three changes in the chemical make-up of a structural protein called desmin in heart muscles in dogs. The changes resulted in the formation of protein clusters, or amyloid-like oligomers, containing desmin, in heart muscle, similar to the amyloid plaques seen in the brains of Alzheimer's patients. These alterations occurred at the onset of heart failure.

In further research by scientists at Johns Hopkins University, these alterations in desmin were found in the heart muscle of four people who had been diagnosed with chronic heart failure.

Mishaped desmin proteins and amyloid-like debris had been previously reported in 2005 in mice that had been genetically modified to develop chronic heart failure. The finding provided the first biological link between the disease and AD. Other studies have also identified desmin changes in failing animal hearts, but "none detailed what the chemical changes were or how they might affect organ function," according to a statement from Johns Hopkins.

The work reported at the AHA meeting is believed to be the first "to tie common underlying structural changes in desmin to malformations observed in the heart as it weakens, strains to pump blood, and starts to fail," the university said. The results of the current work "are also believed to be the first to suggest that toxic, desmin-like amyloids could form in response to stress placed on the heart."

The protein modifications were reversed by surgically repairing the heart.

According to Jenny Van Eyk, director of Johns Hopkins' NHLBI Proteomics Group, and a researcher on the study "what is most surprising about our findings is that we have shown that these chemical changes and debris are related to impaired heart function, which ultimately, may explain why the heart can fail."

Van Eyk is also the director of the Proteomics Center at Johns Hopkins Bayview Medical Center, where the protein analysis work was done.

The work was made possible only within the last 15 years with technologies such as mass spectrometry and gel electrophoresis, which allows for detailed chemical analysis, said Giulio Agnetti, the lead investigator on the study and a protein biochemist. Agnetti is a post-doc research fellow at the Johns Hopkins University School of Medicine and its Heart and Vascular Institute, and the University of Bologna in Italy and its National Institute of Cardivascular Research.

"Now we have a chemical target to research further and help us investigate what could be the underlying biological cause of heart failure, and if it is like Alzheimer's," he said, adding that the study raises the prospect of testing new treatment options.

In ongoing work, the researchers will analyze each of the desmin alterations to determine the subsequent biological impact of each chemical change.

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