Abstract
In recent years, several studies have suggested that cardiometabolic disorders, such as diabetes, obesity, hypertension, and dyslipidemia, share strong connections with the onset of neurodegenerative disorders such as Parkinson’s and Alzheimer’s disease (AD). However, establishing a definitive link between medical disorders with coincident pathophysiologies is difficult due to etiological heterogeneity and underlying comorbidities. For this reason, amyloid β (Aβ), a physiological peptide derived from the sequential proteolysis of amyloid precursor protein (APP), serves as a crucial link that bridges the gap between cardiometabolic and neurodegenerative disorders. Aβ normally regulates neuronal synaptic function and repair; however, the intracellular accumulation of Aβ within the brain has been observed to play a critical role in AD pathology. A portion of Aβ is believed to originate from the brain itself and can readily cross the blood-brain barrier, while the rest resides in peripheral tissues that express APP required for Aβ generation such as the liver, pancreas, kidney, spleen, skin, and lungs. Consequently, numerous organs contribute to the body pool of total circulating Aβ, which can accumulate in the brain and facilitate neurodegeneration. Although the accumulation of Aβ corresponds with the onset of neurodegenerative disorders, the direct function of periphery born Aβ in AD pathophysiology is currently unknown. This review will highlight the contributions of individual cardiometabolic diseases including cardiovascular disease (CVD), type 2 diabetes (T2D), obesity, and non-alcoholic fatty liver disease (NAFLD) in elevating concentrations of circulating Aβ within the brain, as well as discuss the comorbid association of Aβ with AD pathology.
Highlights
Cardiometabolic disease (CMD) pathology is a complex subject due to the intersection of various metabolic, genetic, behavioral, and environmental factors (Stanhope et al, 2018)
The objective of this review is to explore how major cardiometabolic diseases (T2D, obesity, and non-alcoholic fatty liver disease (NAFLD)) contribute to Alzheimer’s disease (AD) pathology
As a consequence of the substantial effects that cardiometabolic modifications can have on amyloid β (Aβ) metabolism, Aβ will be the component of AD pathology central to this review
Summary
Cardiometabolic disease (CMD) pathology is a complex subject due to the intersection of various metabolic, genetic, behavioral, and environmental factors (Stanhope et al, 2018). As a consequence of the substantial effects that cardiometabolic modifications can have on Aβ metabolism, Aβ will be the component of AD pathology central to this review Due to their etiological similarities, T2D and obesity-induced conditions, including hyperinsulinemia, insulin resistance, hyperglycemia, altered insulin signaling, and inflammation, and their relationship with Aβ metabolism will be discussed concurrently. On a separate but related matter, liver fat accumulation is understood to exacerbate inflammation, contributing to the overactivation of hormonal production sites, such as the Islets of Langerhans (Yoon et al, 2017) This hormonal overactivation can lead to abnormal metabolic activity that reduces pancreatic and digestive functionality but favors overproduction of insulin from the pancreas, exacerbating conditions of increased circulating insulin that typifies chronic hyperinsulinemia (Yoon et al, 2017).
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