Tangled proteins link diseases of the heart and brain

Illustration of neurons with amyloid plaques in Alzheimer's disease

Misfolded proteins can wreak havoc in both heart failure and Alzheimer’s disease, but this link may allow heart biomarkers to serve as a diagnostic window to the brain

by Shawn Oberrath 

Proteins are meant to be folded intricately into sophisticated functional shapes that are encoded by genetics and influenced by the environment. 

But when something goes awry in certain proteins during the complex enfolding process, the resulting tangle can cause numerous forms of disease, termed proteinopathies, that affect millions of people: Alzheimer’s disease (AD), Parkinson’s disease, cystic fibrosis, and even heart failure. 

Federica del Monte, M.D., Ph.D., a professor in the Division of Cardiology within the MUSC College of Medicine and director of the Christie Heart and Brain Program for Degenerative Diseases and Aging, has been studying the link between diseases of the heart and brain for more than 20 years and was among the first to discover the role of misfolded proteins in heart disease. 

“Over the past two decades, we’ve found that the same plaques that accumulate in the brain in Alzheimer’s disease also accumulate in the heart,” said del Monte. “And they are made of the same protein material, pointing to the same pathogenesis for both organs.” 

Heart failure and AD are among the most common age-related diseases, with heart failure affecting more than 6 million Americans and AD affecting another 6 million, and the numbers continue to climb as the population ages. 

It was already well known that shared risk factors like age, genetics, social factors and protein characteristics can predispose individuals toward heart failure and AD. But a deeper link has also been shown: dementia can occur in patients with heart failure, and vice versa, about a third of the time. 

It is thus an unfortunate given that many of the millions affected by either disease actually suffer from both. 

While the cognitive decline in patients with heart failure was first attributed only to a lack of blood flow to the brain, del Monte and her colleagues dug deeper in their research. Their work led to the discovery of the same types of amyloid plaques in the brains and hearts of AD patients and suggested a new perspective on AD as a systemic disease. 

This new perspective and the link between the heart and the brain may be the keys to less invasive and more effective diagnostic and treatment options for patients with AD. 

Many paths forward

While basic science researchers continue to define the pathology and mechanisms of proteinopathies at the cellular level, we are at a flex point where numerous paths can be pursued, including clinical trials with patients, a groundbreaking multidisciplinary institute, and using the heart as a window to the usually inaccessible brain.  

Diagram of brain and heart with inset microscopic images 
Both brains and hearts of AD patients can show amyloid plaques in microscopy images. Credit: del Monte lab, MUSC.

 For starters, del Monte will be plunging ahead with a clinical study beginning this year, working with collaborators in India, Italy and the United States. These centers will recruit a prospective population of about 150 patients with AD and heart disease in order to characterize their cardiac and cognitive function clinically and to collect samples for biomarker discovery. 

“We’re aiming to partner with collaborators around the world so we can understand whether this is applicable to the population as a whole,” said del Monte. “And ideally we’ll include some African populations as well so we can see whether there are racial differences.” 

As mentioned above, del Monte heads up the Christie Heart and Brain Program for Degenerative Diseases and Aging, which offers a structure and funding for studying the linked diseases as well as offering care to patients in the hospital. She and her colleagues in the MUSC Division of Cardiology are working toward expanding the program into a multidisciplinary institute that will look holistically at patients while continuing to blend clinical and translational research.

Federica del Monte, M.D., Ph.D. 
Frederica del Monte, M.D., Ph.D., studies the links between heart and brain. Credit: Sarah Pack.

“Down the road we would like to establish a clinic where cardiologists, neurologists with expertise in heart failure and cognitive disorders, psychologists and physical therapists can all work with a patient in one place,” she said. 

The planned institute will also support families and caregivers through the challenges that come with age-related degenerative diseases, which can include emotional suffering, loss of pay or career status, and loss of social connections outside the home. 

“It's scary for patients who are confused about where they are and who they are, and it’s scary for caregivers to think that in addition to dementia, their relative may have a cardiac problem or cardiac emergencies,” del Monte said. “The burden is heavy.” 

One promising intervention that del Monte hopes will bear fruit quickly is a collaboration with MUSC’s Wellness Center to establish an exercise program for patients with dementia and heart failure. Such an approach is the only effective therapy for AD for now, and similar targeted exercise programs have been effective for patients with Parkinson’s disease. 

Finally, researchers will continue to use basic research to seek better diagnostic and treatment options for patients with AD. If they can find a specific biomarker held in common between the heart and the brain, they can access it through the blood or urine and gain a picture of what is happening in the brain before leaning on more invasive techniques like PET imaging or MRI. 

MUSC has also worked with researchers at the University of Texas Medical Branch to patent an antibody treatment that works in both the brain and heart in an animal model. If it continues to be successful, it may be able to progress to clinical trials in humans: “And of course by that time we will have an established clinic, a patient population and hopefully a biomarker.” 

The problem of tangled proteins in human health will persist, but there are many avenues to explore to find help for people with the debilitating diagnosis of AD, and del Monte plans to use them all. “Our goal is to treat patients as early as possible, diagnose them as early as possible, give them some relief, and support their families.”