Complement Gene Single Nucleotide Polymorphisms and Biomarker Endophenotypes of Alzheimer's Disease

Article type: Research Article

Authors: Daborg, Jonny^a | Holmgren, Sandra^b | Abramsson, Alexandra^b | Andreasson, Ulf^b | Zetterberg, Madeleine^c | Nilsson, Staffan^d | Minthon, Lennart^e | Skoog, Ingmar^b | Blennow, Kaj^b | Pekna, Marcela^f | Hanse, Eric^a | Zetterberg, Henrik^{b; g; *}

Affiliations: [a] Institute of Neuroscience and Physiology, Department of Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden | [b] Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden | [c] Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation/Ophthalmology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden | [d] Institute of Mathematical Sciences, Department of Mathematical Statistics, Chalmers University of Technology, Gothenburg, Sweden | [e] Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden | [f] Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden | [g] UCL Institute of Neurology, Queen Square, London, UK

Correspondence: [*] Correspondence to: Henrik Zetterberg, MD, PhD, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, S-431 80 Mölndal, Sweden. Tel. (secretary): +46 31 3430025; Fax: +46 31 3432426; E-mail: henrik.zetterberg@gu.se.

Abstract: The complement system has been implicated in both physiological synapse elimination and Alzheimer's disease (AD). Here, we investigated associations between four single nucleotide polymorphisms (SNPs) in complement genes and cerebrospinal fluid (CSF) biomarkers for AD in 452 neurochemically or neuropathologically verified AD cases and 678 cognitively normal controls. None of the SNPs associated with risk of AD but there were potential associations of rs9332739 in the C2 gene and rs4151667 in the complement factor B gene with CSF tau levels (p = 0.023) and Mini-Mental State Examination scores (p = 0.012), both of which may be considered markers of disease intensity/severity.

Keywords: Alzheimer's disease, complement, microglia, single nucleotide polymorphisms

DOI: 10.3233/JAD-121930

Journal: Journal of Alzheimer's Disease, vol. 35, no. 1, pp. 51-57, 2013