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 (Aβ_1–42, Aβ_1–40, Aβ_1–38) 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 (Aβ_1–38, Aβ_1–40, Aβ_1–42) did not differ between disease groups. Independently of disease group, the Aβ_1–38 levels correlated with Aβ_1–40 and Aβ_1–42 (p<0.001, n=277). Notably the ratio Aβ_1–42 to Aβ_1–38 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 Aβ_1–40 (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.