Alzheimer's disease and age-related macular degeneration have different genetic models for complement gene variation

• Published in: Neurobiology of aging 2012-08, Vol.33 (8), p.1843.e9-1843.e17
• Main Authors: Proitsi, Petroula, Lupton, Michelle K, Dudbridge, Frank, Tsolaki, Magda, Hamilton, Gillian, Daniilidou, Makrina, Pritchard, Megan, Lord, Kathryn, Martin, Belinda M, Craig, David, Todd, Stephen, McGuinness, Bernadette, Hollingworth, Paul, Harold, Denise, Kloszewska, Iwona, Soininen, Hilkka, Mecocci, Patrizia, Velas, Bruno, Gill, Michael, Lawlor, Brian, Rubinsztein, David C, Brayne, Carol, Passmore, Peter A, Williams, Julie, Lovestone, Simon, Powell, John F
• Format: Article
• Language: English
• Subjects: Age; Age-related macular degeneration (AMD); Aged; Aged, 80 and over; Aging; Alzheimer Disease - genetics; Alzheimer's disease; Alzheimer's disease (AD); Comorbidity; Complement activation; Complement component C2; Complement component C3; Complement factor B; Complement factor H; Complement pathway; Complement Pathway, Classical - genetics; Complement System Proteins - genetics; Europe - epidemiology; Female; Genetic Markers - genetics; Genetic models; Genetic Predisposition to Disease - epidemiology; Genetic Predisposition to Disease - genetics; Genetic Variation; Humans; Internal Medicine; Macular Degeneration; Male; Middle Aged; Nervous system; Neurodegenerative diseases; Neurology; Polymorphism, Single Nucleotide - genetics; Prevalence; Risk Assessment; Risk factors; Siblings; Single nucleotide polymorphisms (SNPs); Single-nucleotide polymorphism
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2011.12.036

Abstract Alzheimer's disease (AD) and age-related macular degeneration (AMD) are both neurodegenerative disorders which share common pathological and biochemical features of the complement pathway. The aim of this study was to investigate whether there is an association between well replicated AMD genetic risk factors and AD. A large cohort of AD ( n = 3898) patients and controls were genotyped for single nucleotide polymorphisms (SNPs) in the complement factor H (CFH), the Age-related maculopathy susceptibility protein 2 (ARMS2) the complement component 2 (C2), the complement factor B (CFB), and the complement component 3 (C3) genes. While significant but modest associations were identified between the complement factor H, the age-related maculopathy susceptibility protein 2, and the complement component 3 single nucleotide polymorphisms and AD, these were different in direction or genetic model to that observed in AMD. In addition the multilocus genetic model that predicts around a half of the sibling risk for AMD does not predict risk for AD. Our study provides further support to the hypothesis that while activation of the alternative complement pathway is central to AMD pathogenesis, it is less involved in AD.