Alzheimer's disease and age-related macular degeneration have different genetic models for complement gene variation.
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.
King's College London, Institute of Psychiatry, De Crespigny Park, London, UK. petroula.proitsi@kcl.ac.uk
Petroula
P
Proitsi
Michelle K
MK
Lupton
Frank
F
Dudbridge
Magda
M
Tsolaki
Gillian
G
Hamilton
Makrina
M
Daniilidou
Megan
M
Pritchard
Kathryn
K
Lord
Belinda M
BM
Martin
Janet
J
Johnson
David
D
Craig
Stephen
S
Todd
Bernadette
B
McGuinness
Paul
P
Hollingworth
Denise
D
Harold
Iwona
I
Kloszewska
Hilkka
H
Soininen
Patrizia
P
Mecocci
Bruno
B
Velas
Michael
M
Gill
Brian
B
Lawlor
David C
DC
Rubinsztein
Carol
C
Brayne
Peter A
PA
Passmore
Julie
J
Williams
Simon
S
Lovestone
John F
JF
Powell
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D015897:Comorbidity; D003171:Complement Pathway, Classical / Q000235:genetics*; D003165:Complement System Proteins / Q000235:genetics*; D005060:Europe / Q000453:epidemiology; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D008268:Macular Degeneration; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D018570:Risk Assessment
D005819:Genetic Markers; D003165:Complement System Proteins