Getting to the Heart of Alzheimer Disease

Abstract

In a somewhat narrow diagnostic lens, Alzheimer’s Disease (AD) has been considered a brain specific disease characterized by the presence of β-Amyloid plaques and tau neural fibrillary tangles and neural inflammation; these pathologies lead to neuronal death and consequently clinical symptoms such as memory loss, confusion, and impaired cognitive function. However, for decades researchers have noticed a link between various cardiovascular abnormalities and AD - such as heart failure (HF), coronary artery disease (CAD), atrial fibrillation (AF), and vasculopathy. A considerable volume of work has pointed at this head to heart connection, focusing mainly on associations between cerebral hypoperfusion and neuronal degradation. However, new evidence of a possible systemic or metastatic profile to AD calls for further analysis of this connection. β amyloid aggregations - biochemically and structurally akin to those found in the typical AD pathology - are now known to be present in the hearts of individuals with idiopathic dilated cardiomyopathy (iDCM) as well as the hearts of patients with AD. These findings suggest a potential systemic profile of proteinopathies, and a new hypothesis for the link between peripheral and central symptoms of HF and AD. Herein, we provide an overview of the cardiovascular links to Alzheimer’s disease.

Integrative Multi-Omics Analysis in Calcific Aortic Valve Disease Reveals a Link to the Formation of Amyloid-Like Deposits

“…The majority of these genes are known to participate in amyloid plaque formation and neurodegenerative disorders. Our novel network points towards a previously emerged link between cardiovascular disease and Alzheimer’s disease [ 54 ]. Indeed, Alzheimer’s disease revealed one of the highest betweenness in our multi-integration approach.…”

Intracellular Calcium Dysregulation by the Alzheimer’s Disease-Linked Protein Presenilin 2

“…Importantly, abnormal protein oligomers/aggregates have been reported to disturb Ca 2+ homeostasis and contribute to the cardiac pathology [90]. Thus, the common regulatory mechanism behind the convergence between AD and cardiac diseases could be the Ca 2+ dysfunction [87] but the field is open to new hypotheses [91].…”

Protection from the Pathogenesis of Neurodegenerative Disorders, including Alzheimer’s Disease, Amyotrophic Lateral Sclerosis, Huntington’s Disease, and Parkinson’s Diseases, through the Mitigation of Reactive Oxygen Species

“…Alzheimer disease is a brain-speci ic disorder characterized by the presence of tau NFT, neural in lammation, and Aβ plaques [51][52][53]. These pathologies cause neuronal death and concomitant clinical symptoms, such as confusion, impaired cognitive function, and memory loss [54][55][56]. One of the key characteristics of AD is the substantial and progressive erosion of neurons in the cortex [57].…”

“…An imbalance between ROS production and the activities of enzymes responsible for ROS scavenging results in increased oxidative damage in AD patients [54]. Numerous studies have demonstrated that OS and ROS have a signi icant role in AD by causing deleterious effects to proteins and other important biomolecules [20,60].…”

“…These oxidized proteins accumulate in the cytoplasm of neurons to create Aβ plaques, which serve to propagate the cycle of oxidative damage via increasing ROS levels [63,64]. Another contribution of OS to AD is through mitochondrial dysfunction caused by the accumulation of the Aβ aggregates [54]. In this regard, mitochondrial dysfunction is a key protagonist in the pathogenesis of AD [12,65,66].…”