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

Abstract

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.

Subclinical Cardiac Dysfunction and Brain Health in Midlife: CARDIA (Coronary Artery Risk Development in Young Adults) Brain Magnetic Resonance Imaging Substudy

“…31 Recent studies report that patients with dementia are predominantly affected by heart failure with preserved ejection fraction and diastolic cardiac dysfunction, indicating its relevance for and possible influence on brain health. 32,33 A new paradigm of heart failure with preserved ejection fraction proposed that conditions such as high blood pressure, obesity, diabetes mellitus, and other comorbidities induce a systemic inflammatory state. 34 This affects the coronary endothelium and triggers its dysfunction, which contributes to cardiac remodeling and eventually results in diastolic heart failure.…”

Exosome release and cargo in Down syndrome

“…For example, Aβ aggregates, generally thought to be specific to brain tissue, have also been found in the skin, skeletal muscle and gut tissue of AD patients (Joachim, Mori, & Selkoe, 1989). Additionally, it has been discovered that Aβ aggregates are present in the myocardium of patients with AD (Troncone et al, 2016). The occurrence of Aβ deposits in multiple tissues suggests that the protein may be either produced locally in numerous organs or derived from a common circulating precursor (Jensen & Willis, 2016).…”

Pathophysiology

“…Echocardiographic measurements of myocardial function suggest that patients with Alzheimer's disease (AD) present with an anticipated diastolic dysfunction. As in the brain, A β40 and A β42 are present in the heart, and their expression is increased in AD [14]. • RAS-MAPK pathway disruption: Mutations in RAF-1 gene are responsible for rare variants of childhood-onset, non-syndromic DCM.…”