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

King's College London, Institute of Psychiatry, De Crespigny Park, London, UK.
Neurobiology of aging (Impact Factor: 5.01). 01/2012; 33(8):1843.e9-17. DOI: 10.1016/j.neurobiolaging.2011.12.036
Source: PubMed


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.


Available from: Kathryn Lord, Aug 27, 2015
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    • "Aging, hypercholesterolemia, hypertension, obesity, arteriosclerosis, and smoking are risk factors for AMD and AD [22-24]. Nevertheless, the genetic risk factors in AMD and AD seem to have different origins, although polymorphisms in the apolipoprotein E and complement factor H genes have shown effects on the risks for AMD and AD [21-25,29]. Our study provided further support to the hypothesis that although the rs2075650 polymorphism is associated with AD [15,18,19], this polymorphism is not involved in nAMD. "
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