Key result
Amyloid-β drives cardiac dysfunction by suppressing BDNF and promoting myocardial denervation.
Why the study?
It remained unclear whether Alzheimer's disease pathology has a direct effect on cardiac function and myocardial innervation.
Does Alzheimer's disease pathology and Amyloid β deposition reduce cardiac neurotrophic signaling and cause cardiac dysfunction in preclinical and post-mortem human models?
Does Alzheimer's disease pathology and Amyloid β deposition reduce cardiac neurotrophic signaling and cause cardiac dysfunction in preclinical and post-mortem human models?
This study identifies a novel pathophysiological mechanism by which Alzheimer's-associated Amyloid β pathology directly compromises cardiac neurotrophic signaling, linking neurodegeneration to heart disease.
Hypothesis-generating for amyloid-driven cardiac denervation in Alzheimer's models; leaves open human translation and clinical relevance.
While a link between cardiovascular risk factors and increased Alzheimer's disease (AD) risk has been reported, it remains unclear whether AD pathology has a direct effect on cardiac function and myocardial innervation. AD and amyloidosis are known to impair neuronal function and affect brain neurotrophic factors (NGF and BDNF) expression. Amyloid aggregates and neuro‐signaling impairments may also expose AD patients to peripheral nervous system deficits, promoting cardiac disorders. Here, we provide novel understanding of cardiac physiological impairment, amyloid pathology, neurotrophic factors loss, and impoverishment of cardiac neuronal fibers in Tg2576‐AD mice hearts, human cardiomyocytes in culture, and human AD post‐mortem left ventricular (LV) heart tissue. We reveal that Tg2576 animals exhibit increased myocardial fibrosis, amyloid β (Aβ) deposition, and brain/heart‐axis neurotrophic deficiencies, resulting in myocardial denervation and cardiac dysfunction. Aβ oligomers challenge reduces BDNF expression in both human immortalized and iPSC‐derived cardiomyocytes, by disrupting TrkB/CREB signaling. Analysis of human LV AD post‐mortem tissue confirms cell and animal results. Our findings reveal potential pathways by which Aβ pathology may disrupt cardiac neurotrophic signaling and physiology, identifying a possible link between AD and heart degeneration.
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Elia et al. (2026) studied Alzheimer's disease-associated heart disease (n=11). Amyloid β deposition (Alzheimer's disease pathology) vs. Wild-type mice and healthy post-mortem human donors was evaluated on Cardiac physiological impairment and neurotrophic factor expression (BDNF, NGF, GAP-43). Alzheimer's disease pathology, specifically Amyloid β deposition, instigates cardiac neurotrophic signaling impairment by reducing BDNF expression, driving myocardial denervation and cardiac dysfunction.
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