Short report Monocyte chemoattractant protein-1 (MCP-1) gene polymorphism and risk of Alzheimer’s disease in Italians Roberto Pola * , Andrea Flex, Eleonora Gaetani, Anna S. Proia, Pierangelo Papaleo, Angela Di Giorgio, Giuseppe Straface, Giovanni Pecorini, Michele Serricchio, Paolo Pola Laboratory of Vascular Biology and Genetics, Department of Medicine, A. Gemelli University Hospital, Universita ` Cattolica del Sacro Cuore School of Medicine, Rome, Italy Received 24 February 2004; received in revised form 3 May 2004; accepted 4 May 2004 Available online 31 May 2004 Abstract Monocyte chemoattractant protein-1 (MCP-1) is a key molecule for monocyte chemotaxis and tissue extravasation and for the modulation of leukocyte function during inflammation. Upregulation of MCP-1 may occur in the brain of subjects affected by Alzheimer’s disease (AD) and MCP-1 levels in plasma and cerebrospinal fluid have been proposed as biological markers for the inflammatory process that accompanies AD pathogenesis. Importantly, serum levels and biological activity of MCP-1 protein are strongly influenced by a single nucleotide polymorphism occurring at position 2 2518 of the MCP-1 gene promoter. A recent study has investigated the possible association between this gene polymorphism and AD in a Spanish population, with negative results. Here, we performed a case – control study to test whether the risk for AD might be influenced by the 2 2518 A/G polymorphism of the MCP-1 gene in an ethnically homogeneous Italian population. The GG genotype and the G allele of the MCP-1 gene polymorphism were significantly more common in the AD group than in control individuals ðP , 0:0001Þ: A logistic regression analysis indicated that the GG genotype was an independent risk factor for AD in our population. This effect was not influenced by the presence of the APOE 14 high-risk allele, nor by the presence of other gene variations associated with a pro- inflammatory phenotype. These findings indicate that the 2 2518 A/G polymorphism of the MCP-1 gene is associated with AD in Italians and confirm that inflammatory gene variations may be important contributors in the development and progression of neurodegenerative disorders. q 2004 Elsevier Inc. All rights reserved. Keywords: MCP-1; Gene polymorphism; Inflammation; Alzheimer’s disease 1. Introduction A considerable body of evidence supports the notion that various inflammatory mediators, including cytokines, chemokines, and adhesion molecules, are involved in the initiation and progression of neurodegeneration in Alzhei- mer’s disease (AD) (Lee et al., 2002). Indeed, in this pathologic condition, the initial injurious inflammatory stimulus is thought to be the deposition of insoluble extracellular aggregates of amyloid-beta (A-beta) fibrils, that leads to an innate host response characterized by the upregulation of inflammatory mediators and the accumu- lation of activated microglia (Dickson et al., 1988). In this scenario, it appears obvious that molecules that are able to modulate recruitment, migration, accumulation, and acti- vation of monocytes into sites of tissue injury may be crucial for the initiation of the inflammatory process responsible for neurodegeneration (Luster, 1998). A key molecule for monocyte chemotaxis and tissue extravasation and for modulation of leukocyte function during inflam- mation is the monocyte chemoattractant protein-1 (MCP-1), a potent chemokine for which an important contribution in the pathogenesis of autoimmune diseases, chronic inflam- matory disorders, and neuroinflammatory phenomena has already been proposed (Luster, 1998; Izikson et al., 2002; Muhlbauer et al., 2003; Gerard and Rollins, 2001). The potential role of MCP-1 in the pathogenesis of AD is supported by the fact that MCP-1 may be upregulated in the brains of subjects affected by AD and that plasma and cerebrospinal fluid MCP-1 levels might be used as biological markers of the inflammatory process that accompanies the development of AD (Sun et al., 2003). 0531-5565/$ - see front matter q 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.exger.2004.05.001 Experimental Gerontology 39 (2004) 1249–1252 www.elsevier.com/locate/expgero * Corresponding author. Address: Istituto di Patologia Speciale Medica, Laboratory of Vascular Biology and Genetics, L.go A. Gemelli, 8, 00168 Rome, Italy. Tel.: þ39-06-30154518; fax: þ39-06-35500486. E-mail address: rob_pola@hotmail.com (R. Pola).