Alzheimer's-Related Amyloid Found in the Heart

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Amyloid beta protein accumulation was present in the hearts of patients with Alzheimer’s disease.
Amyloid beta protein accumulation was present in the hearts of patients with Alzheimer’s disease.

Amyloid beta protein accumulation was discovered in the hearts of patients with Alzheimer's disease, according to the results of a retrospective cross-sectional study published in the Journal of the American College of Cardiology.

Federica del Monte, MD, of Beth Israel Deaconess Medical Center in Boston, and colleagues, sought to determine whether the presence of amyloid beta protein aggregates in these patients would affect myocardial function. 

“Reduced blow flow to the brain from low cardiac output has been linked to cognitive impairment in [heart failure],” the researchers explained. “Here, we analyzed whether, conversely, myocardial function is abnormal in [Alzheimer's disease].”

The cohort consisted of both Alzheimer's cases and controls and was matched by age, sex, and ethnicity in a 1:2 ratio. The researchers used myocardial tissue and brain samples for imaging and molecular tests. Patients who had histories of coronary artery disease, previous myocardial infarction, hypertension, primary or secondary amyloidosis, dilated or hypertrophic cardiomyopathy, endocarditis, chemotherapy, or radiotherapy were excluded since these conditions also affect myocardial function.

After conducting a linear regression analysis, the researchers found that age predicted a reduction in diastolic function by mitral valve E/A ratio. Patients were divided into 3 age groups (younger than 65 years of age, 65 to 80 years of age, and older than 80 years of age) to analyze means and standard errors of the mean by age category and Alzheimer's disease status. Diastolic function did not differ in the oldest category of age in those patients with Alzheimer's vs controls (E/A ratio: 0.82 ± 0.08 vs 0.86 ± 0.08). In the youngest age category, however, there was an association between Alzheimer's and myocardial function decline (1.20 ± 0.18 vs 1.34 ± 0.12).

The authors noted that this pattern was probably explained by “defects in myocardial compliance” because it was not evident for the atrial component of the mitral valve E/A ratio. A linear regression F test demonstrated this trend was consistent with worse diastolic function at younger ages among patients with Alzheimer's disease.

In addition, the difference in left ventricular (LV) wall thickness was only significant in the oldest category of patients (LV septal wall thickness: 1.12 ± 0.05 vs 1.01 ± 0.04; P <.05; LV inferolateral wall thickness: 1.07 ± 0.05 vs 1.00 ± 0.03; P <.05) and not in the youngest category, which means it was not a cause of diastolic dysfunction in patients younger than 65 years of age.

These findings highlight the importance of understanding the heart's pathological involvement in Alzheimer's disease. “As the heart is exposed to the free circulatory flow of aggregate-prone peptides, and no barrier segregates the organ,” the researchers wrote, “the involvement of this ‘nonimmunoprivileged' organ may carry a worse prognosis is the case with cardiac AL amyloidosis.”

They concluded that the combination of Alzheimer's and heart failure requires an interdisciplinary approach to effectively manage and treat patients.

Study Limitations

  • Only a small number of samples were available for clinical, pathological, and molecular biology assessment.
  • Alzheimer's disease diagnosis is anatomopathological—obtained from the middle frontal gyrus, inferior parietal lobule, occipital cortex, and the hippocampus/entorhinal cortex. However, this study used brain samples from the cortex. The researchers noted that the amyloid beta pathology tends to spread outside of the hippocampus and entorhinal cortex at such late stages; therefore the regions studied were probably representative of Alzheimer's diagnosis.
  • Not all of the specimens had detailed clinical assessments of cardiac function.
  • E/E' ratio is a more accurate index of diastolic function by echocardiography.

Reference

Troncone L, Luciani M, Coggins M, et al. Amyloid beta pathology affects the hearts of patients with Alzheimer's disease. J Am Coll Cardiol. 2016;68(22):2395-2407. doi:10.1016/j.jacc.2016.08.073.

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