title: 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.
authors.affiliation: Prince of Wales Medical Research Institute, Barker Street, Randwick, Sydney, Australia.
authors.forename: Anna
authors.initials: A
authors.lastname: Sokolova
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Hill
authors.forename: Farid
authors.initials: F
authors.lastname: Rahimi
authors.forename: Lolita A
authors.initials: LA
authors.lastname: Warden
authors.forename: Glenda M
authors.initials: GM
authors.lastname: Halliday
authors.forename: Claire E
authors.initials: CE
authors.lastname: Shepherd
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D018932:Chemokine CCL2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D015850:Interleukin-6; D016209:Interleukin-8