Author + information
- Received July 5, 2016
- Revision received August 8, 2016
- Accepted August 31, 2016
- Published online December 6, 2016.
- Luca Troncone, PhDa,
- Marco Luciani, MDa,
- Matthew Coggins, MDa,
- Elissa H. Wilker, ScDa,b,
- Cheng-Ying Ho, MD, PhDc,
- Kari Elise Codispoti, MDc,
- Matthew P. Frosch, MD, PhDd,
- Rakez Kayed, PhDe and
- Federica del Monte, MD, PhDa,f,∗ ()
- aCardiovascular Institute, Beth Israel Deaconess Medical Center, Boston, Massachusetts
- bHarvard T.H. Chan School of Public Health, Boston, Massachusetts
- cDepartment of Neurology, Johns Hopkins Hospital, Baltimore, Maryland
- dDepartment of Pathology, Massachusetts General Hospital, Boston, Massachusetts
- eDepartment of Neurology, University of Texas Medical Branch Health, Galveston, Texas
- fDivision of Cardiology Massachusetts General Hospital, Boston, Massachusetts
- ↵∗Reprint requests and correspondence:
Dr. Federica del Monte, Cardiovascular Institute, Beth Israel Deaconess Medical Center, 3 Blackfan Circle E/CLS9–911, Boston, Massachusetts 02215.
Background Individually, heart failure (HF) and Alzheimer’s 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, the authors 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 are unknown.
Objectives Here, the authors investigated whether amyloid beta (Aβ) protein aggregates are present in the hearts of patients with a primary diagnosis of AD, affecting myocardial function.
Methods The authors 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 with 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, the authors provide the first report of the presence of compromised myocardial function and intramyocardial deposits of Aβ in AD patients. 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. 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.
This work was supported by grants from the National Institutes of Health, NHLBI R01HL098468, and the AHA 14IRG18980028 to Dr. del Monte, and by an Italian Society of Cardiology fellowship to Dr. Luciani. Dr. Luciani’s fellowship from the Italian Society of Cardiology is with the contribution of Merck Sharp & Dohme Italia. Dr. Coggins has edited educational content for DynaMed. Dr. Wilker received reimbursement to attend a conference from Servier Laboratories. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Troncone and Luciani contributed equally to this work.
- Received July 5, 2016.
- Revision received August 8, 2016.
- Accepted August 31, 2016.
- American College of Cardiology Foundation