Alzheimer’s disease is most recognized for its gradual erosion of memory and other cognitive abilities—but new research suggests it may also quietly weaken the heart.  

Alzheimer’s disease is most recognized for its gradual erosion of memory and other cognitive abilities—but new research by scientists at Temple University’s Lewis Katz School of Medicine (Katz) suggests it may also quietly weaken the heart.  

In a study that bridges neuroscience and cardiology, Temple scientists led by Silvia Fossati, PhD, Professor of Neural Sciences and Cardiovascular Sciences and Director of the Alzheimer’s Center at Temple, show that the same toxic proteins that accumulate in the brain in Alzheimer’s patients can also disrupt vital survival signals in the heart.  

“While traditionally viewed as a disease of the brain, mounting evidence suggests Alzheimer’s effects extend beyond the central nervous system,” Dr. Fossati explained. “Our latest study confirms this.” 

The findings, reported online February 10 in the journal Advanced Science, raise new concerns about the disease’s hidden cardiac effects.  

Alzheimer’s disease is a growing global health crisis, expected to triple in prevalence by 2050 as populations age. The disease is marked by amyloid-β plaques and tau tangles, which aggregate in the brain, and by widespread vascular damage known as cerebral amyloid angiopathy (CAA). Alzheimer’s pathology also reduces levels in the brain of a substance known as brain-derived neurotrophic factor (BDNF).  

Neurotrophic factors—particularly BDNF—are essential for both neuronal health and proper cardiac function. Although BDNF is present in the heart, whether its levels are altered in the heart in Alzheimer’s patients had never been explored.  

To investigate this, Dr. Andrea Elia, a postdoctoral fellow in Dr. Fossati’s laboratory and first author of the study, and the other Temple researchers examined the hearts of Tg2576 mice, a widely used model of Alzheimer’s-related amyloidosis. They found that as amyloid-β accumulated, the animals developed progressive cardiac dysfunction, including increased heart mass, fibrosis, and reduced contractility. These changes were accompanied by a marked loss of cardiac nerve fibers and significantly lower levels of neurotrophic factors such as BDNF. 

Cell culture experiments provided further insight. When human cardiomyocytes and neural cells were exposed to toxic amyloid-β molecules, BDNF levels dropped sharply. The team traced this effect to the suppression of CREB, a key pro-survival signaling molecule downstream of the BDNF receptor TrkB. Importantly, activating TrkB helped protect heart cells from amyloid-β-induced cell death, pointing to a potential therapeutic target. The findings were reinforced by analyses of post-mortem heart tissue from individuals with Alzheimer’s disease and CAA, which showed similar neurotrophic signaling deficits. 

“Our results suggest that Alzheimer’s-related amyloid pathology can impair cardiac neuro-signaling, potentially weakening the heart through the loss of neurotrophic support,” Dr. Fossati said. “This fills a critical knowledge gap, highlighting a previously underappreciated heart-brain connection in Alzheimer’s disease.” 

Future research will explore whether therapies aimed at restoring BDNF/TrkB signaling—or preventing toxic amyloid buildup in the heart—could help protect cardiac function in people living with Alzheimer’s disease. “We are at a new frontier in Alzheimer’s research in realizing that the disease may be as much a whole-body disorder as it is a disorder of the brain,” Dr. Fossati added. 

Other researchers who contributed to the new study include Rebecca Parodi-Rullan, Rafael Vazquez-Torres, and Ashley Carey, Alzheimer’s Center at Temple, Department of Neural Sciences, Lewis Katz School of Medicine; Huaqing Zhao, Center for Biostatistics and Epidemiology, Department of Biomedical Education and Data Science, Temple University Lewis Katz School of Medicine; and Sabzali Javadov, Department of Physiology, University of Puerto Rico School of Medicine, San Juan. 

The research was funded in part by grants from the National Institutes of Health, the Alzheimer’s Association, the Pennsylvania Department of Health Collaborative Research on Alzheimer’s Disease, the American Heart Association, the Karen Toffler Charitable Trust, and the Lemole Center for Integrated Lymphatics.