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Basic Science and Pathogenesis
Andrea Elia1, Rebecca M Parodi Rullan2, Rafael Vazquez-Torres3
1Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.
Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
Summary
Alzheimer's disease (AD) pathology disrupts brain-heart signaling, causing cardiac nerve damage and dysfunction. Amyloid-beta (Aβ) oligomers reduce brain-derived neurotrophic factor (BDNF) in heart cells, highlighting a new mechanism for AD-related cardiac issues.
Area of Science:
- Neuroscience
- Cardiology
- Molecular Biology
Background:
- Alzheimer's disease (AD) disrupts neurotrophic factors (NTFs), impacting neuronal health and potentially causing cardiovascular issues.
- Mechanisms linking AD pathology to impaired brain-heart axis, myocardial innervation, and function remain unclear.
Purpose of the Study:
- To investigate the impact of AD pathology on cardiac physiology and the brain-heart axis.
- To elucidate the role of amyloid-beta (Aβ) in neurotrophic factor depletion and cardiac neuronal degeneration.
Main Methods:
- Comprehensive analysis of cardiac physiology, amyloid pathology, NTF depletion, and cardiac neuronal fiber degeneration in AD mouse models, human cardiomyocytes, and human AD heart tissue.
- Assessment of Aβ oligomer effects on BDNF expression and CREB function in cardiomyocytes.
- Postmortem analysis of human left ventricular (LV) tissue from AD patients.
Main Results:
- AD pathology increases myocardial fibrosis, Aβ deposition, and brain-heart axis remodeling, leading to myocardial denervation and impaired cardiac function.
- Aβ oligomers reduce BDNF expression in human cardiomyocytes by disrupting CREB function.
- Human AD LV tissue confirmed findings from animal and cell studies.
Conclusions:
- A previously unrecognized mechanism reveals Aβ dysregulates cardiac neurotrophic signaling, contributing to cardiac degeneration in AD.
- Findings underscore the significance of cardiac complications in AD management and suggest new therapeutic avenues.
- Highlights the need to reevaluate clinical approaches to AD therapy by considering cardiac health.
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