Monocyte chemoattractant protein-1 plays a dominant role in the chronic inflammation observed in Alzheimer's disease

Abstract

Chronic neuroinflammation correlates with cognitive decline and brain atrophy in Alzheimer's disease (AD), and cytokines and chemokines mediate the inflammatory response. However, quantitation of cytokines and chemokines in AD brain tissue has only been carried out for a small number of mediators with variable results. We simultaneously quantified 17 cytokines and chemokines in brain tissue extracts from controls (n = 10) and from patients with and without genetic forms of AD (n = 12). Group comparisons accounting for multiple testing revealed that monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) and interleukin-8 (IL-8) were consistently upregulated in AD brain tissue. Immunohistochemistry for MCP-1, IL-6 and IL-8 confirmed this increase and determined localization of these factors in neurons (MCP-1, IL-6, IL-8), astrocytes (MCP-1, IL-6) and plaque pathology (MCP-1, IL-8). Logistic linear regression modeling determined that MCP-1 was the most reliable predictor of disease. Our data support previous work on significant increases in IL-6 and IL-8 in AD but indicate that MCP-1 may play a more dominant role in chronic inflammation in AD.

Figure 1

Monocyte chemoattractant protein‐1 (MCP‐1) levels (expressed as picogram per milligram protein) in the soluble protein fraction of the inferior temporal cortex of control (young and old) and Alzheimer's disease (AD) [sporadic and presenilin‐1 (PS1)] brains measured with the Bio‐Plex bead‐based immunoassay kit.

Figure 2

Immunohistochemical detection of monocyte chemoattractant protein‐1 (MCP‐1) (A–C), interleukin‐6 (IL‐6) (D–F) and interleukin‐8 (IL‐8) (G–I) in presenilin‐1 (PS1) AD (A,D,G), sporadic AD (B,E,H) and old controls (C,F,I). Immunoreactivity in young and old controls was similar, so only representative cases from old controls are shown. The scale bar (50 µm) applies to all panels. MCP‐1 immunoreactivity was seen in neurons (arrowheads, A,B), astrocytes (arrows, A,B) and plaques (open arrowheads, A,B) in PS1 (A) and sporadic (B) AD. MCP‐1 immunoreactivity was predominantly observed in neurons in controls (arrowhead, C). Within the cortex IL‐6, immunoreactivity was seen in neurons (arrowheads, D,E) as well as astrocytes (arrows, D,E) in PS1 (D) and sporadic (E) AD. IL‐6 immunoreactivity was predominantly located in neurons in controls (arrowhead, F). IL‐8 immunoreactivity was predominantly seen in plaques (open arrowheads, G,H) and neurons (arrowheads, G,H) in PS1 (G) and sporadic (H) AD. IL‐8 immunoreactivity was predominantly located within neurons in controls (arrowhead, I). AD = Alzheimer's disease.