AUTHOR COPY Journal of Alzheimer’s Disease 35 (2013) 121–127 DOI 10.3233/JAD-122044 IOS Press 121 Functional Mannose-Binding Lectin Haplotype Variants are Associated with Alzheimer’s Disease Annica Sj ¨ olander a,∗ , Lennart Minthon b , Lieve Nuytinck c , Eugeen Vanmechelen d , Kaj Blennow e and Staffan Nilsson f a Centre for Culture and Health, Institute of Health and Care Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden b Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden c Clinical Research Center, Faculty for Medicine and Health Sciences, Universiteit Gent, Belgium d Key4AD, Eke, Belgium e Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden f Department of Mathematical Sciences, Chalmers University of Technology and University of Gothenburg, Gothenburg, Sweden Handling Associate Editor: Rita Businaro Accepted 28 December 2012 Abstract. Mannan-Binding lectin (MBL) is a serum lectin and an important constituent of the innate immune system. Processes linked to the innate immune response have previously been implicated in Alzheimer’s disease (AD). MBL is associated with blood vessels in the brain and AD patients demonstrate lower MBL levels in the cerebrospinal fluid compared to controls. We investigated six single nucleotide polymorphisms, linked to MBL deficiency, in the corresponding MBL2 gene in AD patients and controls. Two MBL2 haplotypes, LXP and LYQ, were significantly associated with AD risk (OR = 1.6, p = 0.01 and OR = 1.5, p = 0.02, respectively). The present study is the first investigating MBL2 genotypes and haplotypes in relation to AD. Our findings support that the MBL2 gene impact the disease risk. Keywords: Alzheimer’s disease, cerebrospinal fluid, gene, immune response, Mannan-Binding lectin, single nucleotide polymorphism INTRODUCTION Mannan-Binding lectin (MBL) is a serum lectin and an important constituent of the innate immune system. Processes linked to the innate immune response have previously been implicated in Alzheimer’s disease (AD) by pathological and epidemiological stud- ies. Additionally, genetic evidence suggests that the ∗ Correspondence to: Annica Sj¨ olander, PhD, Centre for Culture and Health, University of Gothenburg, Box 100, 405 30 Gothenburg, Sweden. Tel.: +46 31 7866926; E-mail: annica.sjolander@gu.se. immune system is involved in the etiology of AD [1]. The abnormal processing of the amyloid  protein pre- cursor (APP), which leads to accumulation of the amyloid  peptide, is thought to be the main causing event of the loss of synapses and the neurodegeneration seen in AD [2]. Increasing evidence suggests that the immune system is involved in the processing of APP, clearance of amyloid , and the cellular response to amyloid  [2–5]. The MBL2 gene is located on chromosome 10 (10q11.2-q21), close to one of the genome regions ISSN 1387-2877/13/$27.50 © 2013 – IOS Press and the authors. All rights reserved