Key result
Alzheimer's disease is linked to myocardial amyloid deposits and earlier diastolic dysfunction in younger patients.
Why the study?
Although heart failure and Alzheimer disease share epidemiological, genetic, and pathological features, it was unknown whether patients with a primary diagnosis of AD have cardiac Aβ protein aggregates and myocardial dysfunction.
Does Alzheimer's disease lead to intramyocardial Aβ amyloid accumulation and compromised myocardial diastolic function compared to matched controls?
Cross-Sectional
No
Does Alzheimer's disease lead to intramyocardial Aβ amyloid accumulation and compromised myocardial diastolic function compared to matched controls?
Answers are grounded in this paper and cite their sources.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“None of the 4 patients with evidence of cardiac Aβ deposition in the present study had a history of heart failure (6). The grade 1 or 2 abnormalities in ventricular relaxation identified in the echocardiography cohort are very mild compared with the advanced diastolic dysfunction associated with cardiac amyloidosis and not necessarily expected to lead to clinical manifestations (6).”
“We agree with the investigators that further studies are needed to determine the dysfunctional cardiac phenotype observed in patients with AD. However, we would suggest that potential biomarkers (i.e., plasma neprilysin concentrations) need to be evaluated to characterize dysfunctional cardiac phenotypes in patients with AD. This may help shed light on the complex mechanism of Aβ and neprilysin regulation in the context of the heart-to-brain connection in patients with AD.”
This study provides the first report that Aβ40 and Aβ42 amyloid aggregates deposit in the myocardium of patients with Alzheimer's disease and are associated with early diastolic dysfunction and impaired cardiomyocyte relaxation.
Background Individually, heart failure (HF) and Alzheimer Disease (AD) are severe threats to population health, and their potential coexistence is an alarming prospect. In addition to sharing analogous epidemiological and genetic profiles, biochemical characteristics, and common triggers, we recently recognized common molecular and pathological features between the 2 conditions. Whereas cognitive impairment has been linked to HF through perfusion defects, angiopathy, and inflammation, whether patients with AD present with myocardial dysfunction, and if the 2 conditions bear a common pathogenesis as neglected siblings is unknown. Objectives Here we investigated if amyloid beta (Aβ) protein aggregates are present in the hearts of patients with a primary diagnosis of AD, affecting myocardial function. Methods We examined myocardial function in a retrospective cross-sectional study from a cohort of AD patients and age-matched controls. Imaging and proteomics approaches were used to identify and quantify Aβ deposits in AD heart and brain specimens compared to controls. Cell shortening and calcium transients were measured on isolated adult cardiomyocytes. Results Echocardiographic measurements of myocardial function suggest that patients with AD present with an anticipated diastolic dysfunction. As in the brain, Aβ40 and Aβ42 are present in the heart, and their expression is increased in AD. Conclusions Here we provide the first report of the presence of compromised myocardial function and intramyocardial deposits of Aβ in AD patients. Our 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. AD and HF are both debilitating and life-threatening conditions, affecting enormous patient populations. Our findings underline a previously dismissed problem of a magnitude that will require new diagnostic approaches and treatments for brain and heart disease, and their combination.
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Troncone et al. (2016) conducted a cross-sectional in Alzheimer's Disease. Alzheimer's disease (with intramyocardial Aβ amyloid pathology) vs. Age-, sex-, and ethnicity-matched controls without Alzheimer's disease was evaluated on Diastolic function measured by mitral valve E/A ratio (MVE/A) in the youngest age tertile (<65 years) (p=<0.05). Alzheimer's disease was associated with intramyocardial Aβ40 and Aβ42 deposits and earlier diastolic dysfunction by mitral valve E/A ratio (1.20 vs 1.34 in age <65, p<0.05) compared to controls.
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