Amyloid in the Heart of Alzheimer’s Patients
Are amyloid beta (Aß) protein aggregates present in the hearts of patients with a primary diagnosis of Alzheimer’s disease (AD)?
In this retrospective cross-sectional study from a cohort of 22 AD patients and 35 age-matched controls, the investigators reviewed Doppler echocardiography data to determine myocardial function. Imaging and proteomics approaches were used to identify and quantify Aß deposits in AD heart and brain specimens compared with controls. They measured cell shortening and calcium transients on isolated adult cardiomyocytes using a video edge-detection and dual-excitation system.
Using linear regression analysis and adjusting the associations between AD status and cardiac function for age, the investigators found that age predicts a reduction in diastolic function by mitral valve E/A ratio (MVE/A). They divided the study cohort into three age groups (<65, 65-80, and >80 years of age). They found that a correlation between AD and anticipated decline of myocardial function was present in the first age tertile (1.20 ± 0.18 vs. 1.34 ± 0.12). This appeared to be better explained by defects in myocardial compliance because such a pattern was not shown for the atrial component (A) of the MVE/A. Using a linear regression F-test (p < 0.05), the investigators observed a pattern that was consistent with poorer diastolic function at earlier ages among the AD participants, conforming with the pathogenesis of AD as a disease of anticipated aging. They also found increased left ventricular septal and inferior wall thickness, respectively, in the older AD participants (p < 0.05 for each). Using immunoblotting and enzyme-linked immunosorbent assay (ELISA), the investigators found that like in the brain, Aß40 and Aß42 were present in the heart, and their expression was increased in AD. They also found that AD cardiomyocytes displayed slower velocities of relaxation (R50 [time to 50% relaxation]: 0.272 vs. 0.238) and prolonged Ca2+ transients (time-to-peak: 0.544 vs. 0.151; R90: 0.328 vs. 0.084) compared with controls, indicating a defect in Ca2+ homeostasis.
The authors suggest that AD may be viewed either as a systemic disease or as a metastatic disorder leading to heart, and possibly multiorgan failure.
The findings of this study are provocative in that the authors suggest that amyloid deposition in AD patients may be due to a heart–brain interaction. The next step is prospective studies to better understand this proposed heart–brain interaction in AD patients.
Clinical Topics: Arrhythmias and Clinical EP, Cardio-Oncology, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Acute Heart Failure, Echocardiography/Ultrasound, Sleep Apnea
Keywords: Alzheimer Disease, Amyloid, Amyloid beta-Peptides, Cardiotoxicity, Diastole, Echocardiography, Doppler, Enzyme-Linked Immunosorbent Assay, Geriatrics, Heart Failure, Homeostasis, Immunoblotting, Myocytes, Cardiac, Proteomics
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