Aβ Amyloid Pathology Affects the Hearts of Patients With Alzheimer's Disease

Mind the Heart

Luca Troncone, Marco Luciani, Matthew Coggins, Elissa H. Wilker, Cheng Ying Ho, Kari Elise Codispoti, Matthew P. Frosch, Rakez Kayed, Federica del Monte

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2395-2407
Number of pages13
JournalJournal of the American College of Cardiology
Volume68
Issue number22
DOIs
StatePublished - Dec 6 2016

Fingerprint

Amyloid
Heart Diseases
Alzheimer Disease
Pathology
Heart Failure
Serum Amyloid A Protein
Amyloid beta-Peptides
Brain
Cardiac Myocytes
Proteomics
Population
Siblings
Molecular Biology
Perfusion
Cross-Sectional Studies
Inflammation
Calcium
Health

Keywords

  • amyloidosis
  • cardiomyopathy
  • dementia
  • heart failure
  • protein aggregates

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Troncone, L., Luciani, M., Coggins, M., Wilker, E. H., Ho, C. Y., Codispoti, K. E., ... del Monte, F. (2016). Aβ Amyloid Pathology Affects the Hearts of Patients With Alzheimer's Disease: Mind the Heart. Journal of the American College of Cardiology, 68(22), 2395-2407. https://doi.org/10.1016/j.jacc.2016.08.073

Aβ Amyloid Pathology Affects the Hearts of Patients With Alzheimer's Disease : Mind the Heart. / Troncone, Luca; Luciani, Marco; Coggins, Matthew; Wilker, Elissa H.; Ho, Cheng Ying; Codispoti, Kari Elise; Frosch, Matthew P.; Kayed, Rakez; del Monte, Federica.

In: Journal of the American College of Cardiology, Vol. 68, No. 22, 06.12.2016, p. 2395-2407.

Research output: Contribution to journalArticle

Troncone, L, Luciani, M, Coggins, M, Wilker, EH, Ho, CY, Codispoti, KE, Frosch, MP, Kayed, R & del Monte, F 2016, 'Aβ Amyloid Pathology Affects the Hearts of Patients With Alzheimer's Disease: Mind the Heart', Journal of the American College of Cardiology, vol. 68, no. 22, pp. 2395-2407. https://doi.org/10.1016/j.jacc.2016.08.073
Troncone, Luca ; Luciani, Marco ; Coggins, Matthew ; Wilker, Elissa H. ; Ho, Cheng Ying ; Codispoti, Kari Elise ; Frosch, Matthew P. ; Kayed, Rakez ; del Monte, Federica. / Aβ Amyloid Pathology Affects the Hearts of Patients With Alzheimer's Disease : Mind the Heart. In: Journal of the American College of Cardiology. 2016 ; Vol. 68, No. 22. pp. 2395-2407.
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abstract = "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.",
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