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

Petroula Proitsi, Michelle K. Lupton, Frank Dudbridge, Magda Tsolaki, Gillian Hamilton, Makrina Daniilidou, Megan Pritchard, Kathryn Lord, Belinda M. Martin, J. Johnson, David Craig, Stephen Todd, Bernadette McGuinness, Paul Hollingworth, Denise Harold, Iwona Kloszewska, Hilkka Soininen, Patrizia Mecocci, Bruno Velas, Michael GillBrian Lawlor, David C. Rubinsztein, Carol Brayne, Peter A. Passmore, Julie Williams, Simon Lovestone, John F. Powell

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22 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)1843.e9-17
JournalNeurobiology of Aging
Issue number8
Early online date3 Feb 2012
Publication statusPublished - Aug 2012


  • Alzheimer's disease
  • age-related macular degeneration
  • AMD
  • complement pathway
  • single nucleotide polymorphism
  • SNPs
  • genetic models


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