Detection of Alzheimer Peptides and Chemokines in the Aqueous Humor

Abstract

Purpose Alzheimer disease (AD) and age-related ocular diseases are characterized by inflammation and accumulation of insoluble proteins. We aimed to investigate the detectability and clinical relevance of a panel of AD-related markers, such as Alzheimer peptides and chemokines, in the aqueous humor (AH) samples taken from patients with cataract only, or cataract and 1 other ocular disease. Methods The AH samples were obtained during cataract surgery from patients with cataract only (n=162), cataract and glaucoma (n=21), cataract and exfoliation (PEX) (n=31), cataract and macular degeneration (n=36), and cataract and diabetic retinopathy (n=16). The AD peptides (Aβ1–42, Aβ1–40, Aβ1–38) and chemokines (eotaxin, eotaxin 3, interleukin [IL]-8, inducible protein-10, monocyte chemotactic protein [MCP]-1, MCP-4, macrophage-derived chemokine, macrophage inflammatory protein-1β, thymus and activation-regulated chemokine) were quantified by using multiplex immunoassays. Results The levels of the AH peptides (Aβ1–38, Aβ1–40, Aβ1–42) did not differ between disease groups. Independently of disease group, the Aβ1–38 levels correlated with Aβ1–40 and Aβ1–42 (p<0.001, n=277). Notably the ratio Aβ1–42 to Aβ1–38 differed between PEX and macular degeneration (mean 95% confidence interval [CI] = 8.12 [11.3–3.99] vs 2.23 [2.67–0.52], p=0.003). Among chemokines examined, only MCP-1 and IL-8 were detected in about 90% to 46% of all analyzed (n=266) samples. Higher levels of AH IL-8 were found in the glaucoma group than in cataract only (p=0.011). Independently of disease group, a correlation was observed between AH MCP-1 and IL-8 (rho=0.275, p<0.001, n=266) and between MCP-1 and Aβ1–40 (rho=0.239, p<0.001, n=266). Conclusions Our findings highlight pathologic similarities between AD and eye diseases, and show the potential of modern technologies to detect AD biomarkers in age-related eye diseases.