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Background: Impaired clearance of amyloid-β protein (Aβ) in the peripheral system is a crucial event in the pathogenesis of sporadic Alzheimer's disease (AD). Dysfunctional monocytes with deficient clearance of Aβ and increased secretion of pro-inflammatory factors in the periphery are considered to contribute to AD development. Multiple studies suggest that IL-4 can inhibit the inflammatory response and enhance the expression and activity of cathepsin protease associated with intracellular clearance of Aβ by monocytes. Objective: To investigate the effects of interleukin-4 (IL-4) on Aβ clearance and inflammatory response of monocytes in vitro. Methods: In this study, flow cytometry, confocal microscopy and ELISA techniques were used for measurement of Aβ clearance and its related mechanisms of monocytes. Results: We found that the mean intracellular content and uptake ratios of Aβ42 in total monocytes, as well as in the CD14 + CD16− subset, were enhanced by IL-4, concomitant with the degradation of Aβ42 by monocytes. And IL-4 treatment also increased expression of scavenger receptor CD36 and Macrophage scavenger receptor 1 (MSR1) on monocytes. It was shown that IL-4 increased the Aβ immunoreactive area within lysosomal markers, including early endosome antigen 1 (EEA1), lysosome-associated membrane glycoprotein 1 and 2 (LAMP1 and 2) and Aβ degradative enzymes cathepsin B and S in monocytes, but reduced secretion of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interferon-γ (IFN-γ) by monocytes. Conclusions: Our study supports the role of IL-4 in regulating Aβ clearance and inflammatory response by monocytes, suggesting that IL-4 may have therapeutic potential for AD. [ABSTRACT FROM AUTHOR]

Background: Abnormal intracellular expression and aggregation of α-synuclein (α-syn) is the histopathological hallmark of several neurodegenerative diseases especially Parkinson's disease. However, safe and efficient approaches to clear α-syn remain unavailable. Objective: This study aimed to investigate the process of peripheral catabolism of brain-derived α-syn. Methods: Thirty patients with atrioventricular reentrant tachycardia (AVRT) (left accessory pathways) who underwent radiofrequency catheter ablation (RFCA) were enrolled in this study. Blood was collected via catheters from superior vena cava (SVC), inferior vena cava (IVC) proximal to the hepatic vein (HV), the right femoral vein (FV), and femoral artery (FA) simultaneously during RFCA. Plasma α-syn levels of AVRT patients and soluble α-syn levels of the brain samples were measured using enzyme-linked immunosorbent assay kits. Results: The α-syn concentrations in different locations of veins were divided by time-matched arterial α-syn concentrations to generate the venous/arterial (V/A) ratio. The V/A ratio of α-syn from the SVC was 1.204 (1.069–1.339, 95% CI), while the V/A ratio of α-syn from IVC was 0.831 (0.734–0.928, 95% CI), suggesting that brain-derived α-syn in the arterial blood was physiologically cleared while going through the peripheral organs and tissues. And it was estimated that about half of brain soluble α-syn could efflux and be cleared in the periphery. Moreover, the glomerular filtration rate was found correlated with V-A difference (FA-ICV) (p = 0.0272). Conclusion: Under physiological conditions, brain-derived α-syn could efflux into and be catabolized by the peripheral system. The kidney may play a potential role in the clearance of α-syn. [ABSTRACT FROM AUTHOR]

Aging societies have high incidence rates of Alzheimer's disease (AD). AD is diagnosed at later disease stages and has a poor prognosis, and effective drugs and treatments for AD are lacking. The molecular mechanism of AD is not clear, and current research focuses primarily on amyloid-β (Aβ) deposition and tau protein hyperphosphorylation. Aβ deposition is the most frequently hypothesized initiating factor of AD, and Aβ clearance during the pathogenesis of AD may be an optional strategy to suppress AD development. Monocytes play important roles in the peripheral clearance of Aβ. Therefore, the present review summarizes our current knowledge of the potential roles of infiltrating macrophages, circulating monocytes, and Kupffer cells in the peripheral clearance of Aβ in AD. [ABSTRACT FROM AUTHOR]