Amyloid beta present in the hearts of patients with Alzheimer’s disease
medwireNews: Researchers have identified intramyocardial amyloid beta (Aβ) aggregates and changes in cardiac function among patients with Alzheimer’s disease (AD).
“[This is] the first report of the presence of compromised myocardial function and intramyocardial deposits of Aβ in AD patients,” write study authors Federica del Monte (Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA) and colleagues in the Journal of the American College of Cardiology.
“The findings depict a novel biological framework in which AD may be viewed either as a systemic disease or as a metastatic disorder leading to heart, and possibly multiorgan failure,” they add.
In an analysis of brain and heart tissue from patients who were deceased but maintained on respiratory support, the researchers found that Aβ aggregates were present within cardiomyocytes and the cardiac interstitium from four patients with histopathologically confirmed AD, but were not found in unaffected control patients. Additional molecular tests confirmed that both Aβ peptides – Aβ40 and Aβ42 – were present in patients with AD.
Cardiomyocytes isolated from the heart of one patient with AD had slower relaxation velocity than those from two control hearts, with time to 50% relaxation measurements of 0.272 versus 0.238 seconds. Similarly, prolonged calcium transients were observed in AD cardiomyocytes (time to peak 0.544 vs 0.151 seconds; time to 90% relaxation 0.328 vs 0.084 seconds).
Although these findings suggest defective calcium homeostasis among cardiomyocytes in AD, the authors caution that “[n]o statistical calculations were performed because we only measured 3 cardiomyocytes from 1 AD case.”
In a separate analysis, the team divided 22 patients with AD and 35 controls into three age groups: younger than 65; 65 to 80; and older than 80 years of age. Although there were no significant differences in diastolic function between participants with and without AD, the mitral valve E/A ratio was numerically lower in those with AD from the youngest age group (1.20 vs 1.34), indicating “poorer diastolic function at earlier ages” among those with AD, which corresponds with “the pathogenesis of AD as a disease of anticipated aging”.
Left ventricular (LV) wall thickness was increased among patients with AD compared with controls, with mean measurements of 1.12 versus 1.01 cm for septal wall thickness and 1.07 versus 1.00 cm for inferolateral wall thickness. However, the difference was only significant among participants more than 80 years old, meaning that LV wall thickness is “not a possible cause of the anticipated diastolic defect found in AD subjects younger than 65 years of age,” say the authors.
In an accompanying commentary, Brian Jensen and Monte Willis, both from the University of North Carolina in Chapel Hill, USA, write that although the findings require confirmation in larger studies, they “represent an intriguing, and potentially paradigm-shifting, advance in our understanding of a highly morbid and largely untreatable disorder.”
They conclude that: “The full clinical implications of the present study remain to be seen, but it is an important step forward in our understanding of the potential cardiac manifestations of common neurodegenerative disorders.”
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