When the Heart Talks to the Brain: Rethinking Cardiovascular-Neurodegenerative Interfaces

Jin Ju* and Zhiguo Wang*

1Department of Pharmacy, the First Affiliated Hospital of Jinan University, Guangzhou 510630, China 2Guangdong Provincial Key Laboratory for Chronic Disease Interactive Network Research, Jinan University, Guangzhou 510632, China

^*Correspondance to: Zhiguo Wang 

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Abstract:

Emerging research reveals a bidirectional interface between cardiovascular diseases—such as atrial fibrillation (AF) and heart failure (HF)—and neurodegenerative disorders, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). While traditional models have emphasized shared risk factors such as aging, chronic inflammation, and metabolic dysfunction, newer evidence points to a more dynamic and causative framework: a reciprocal interactome composed of signaling molecules, extracellular vehicles, and neurohormonal circuits linking cardiac and cerebral systems. Cardiokines (e.g., natriuretic peptides, FGF21), neurokines (e.g., BDNF, NGF), exosomes carrying noncoding RNAs, and systemic axes such as the renin–angiotensin–aldosterone system (RAAS) and hypothalamic–pituitary–adrenal (HPA) axis act as molecular bridges that mediate cross-organ communication. This review shifts focus from risk association to causative molecular dialogue, demonstrating how these interactomes drive remodeling, dysfunction, and progressive degeneration in both systems and repositions the heart–brain axis as a site of active disease–disease interaction, where reciprocal complications emerge from disrupted signaling rather than isolated end-organ pathology. Three clinical vignettes are presented to illustrate the translational relevance of this model. We propose that therapeutic strategies targeting these inter-organs signaling networks— rather than treating individual organ dysfunction in isolation—may offer a more effective and systems-level approach to managing age-related syndromes.

Keywords:

Cardiovascular diseases; Neurodegenerative disorders; Atrial fibrillation; Heart failure; Alzheimer’s disease; Parkinson’s disease; Interactomes; Cardiokines; Neurokines; Exosomes

Cite the Article:

Ju J, Wang Z. When the Heart Talks to the Brain: Rethinking Cardiovascular- Neurodegenerative Interfaces. Ann Clin Case Rep. 2025; 10: 2765..