Genetic Insights into the Impact of Complement in Alzheimer’s Disease
Abstract
:1. Alzheimer’s Disease, Inflammation, and Complement
2. Genetics Implicate Inflammation, Immunity, and Complement in the Pathogenesis of Late-Onset AD
3. Complement Genetic Variation Impacts Risk of Inflammatory Disease
4. Complement in LOAD
5. CR1
5.1. Function
5.2. Expression
5.3. Structure and Genetic Variants
6. Clusterin
6.1. Function
6.2. Expression
6.3. Structure and Genetic Variants
7. C1S
7.1. Function
7.2. Expression
7.3. Genetic Variants
8. Complement in LOAD: Smoking Gun or Red Herring?
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Gene | Variant | Disease |
---|---|---|
C1q | Deficiency Polymorphism | Increased risk of lupus and glomerulonephritis Arthritis, cancer, diabetes, schizophrenia |
C1r/C1s | Deficiency GOF SNP | Autoimmunity, infections, glomerulonephritis, Type I periodontal Ehlers-Danlos Increased risk of AD |
C1INH | Deficiency | Hereditary angioedema (types I and II) |
C2 | Deficiency SNPs | Lupus, bacterial infections Protective for AMD and PCVP |
C3 | GOF Nonsynonymous Coding variant | aHUS, C3G, and AMD |
C4 | Deficiency CNV | Lupus Schizophrenia |
C5 | Nonsense; hom or Compound het | C5 deficiency; neisserial infections |
C6 | Single bp deletion | C6 deficiency; neisserial infections |
C7 | Nonsense: hom or compound het | C7 deficiency; neisserial infections |
C8α | Nonsense: hom or compound het | C8 deficiency, type I; neisserial infections; no C8α protein; free C8β |
C8β | Premature stop codon | C8 deficiency, type II; neisserial infections; no C8β protein; free C8α |
C9 | Nonsense: hom or compound het SNPs | C9 deficiency; neisserial infections AMD; AD |
MASP-1, collectins | Hom/het deficiency | Various developmental; Malpuech, Carnevale, Michels, and Mingarelli syndrome |
Ficolins | SNPs | Rheumatoid arthritis, leprosy, systemic inflammation, bacterial infections |
CFH | Hom deficiency SNPs and truncations | DDD; MPGN C3G; acquired partial lipodystrophy; aHUS AMD; AD; Some protective against meningococcal disease, AMD, IgAN, or C3G |
CFI | Nonsense: hom, het or compound het | AMD; C3G; aHUS; recurrent infections |
MCP | Hom/Het deletion/truncation Missense SNP | Systemic sclerosis, miscarriage, HELLP syndrome, and C3G Severe aHUS; linked to CVID |
CFB | Nonsense: hom or compound het Het GOF SNP Other SNPs | Factor B deficiency; recurrent bacterial infections aHUS Protection against AMD |
Properdin | Nonsense/truncating mutations | Properdin deficiency (X-linked); neisserial infections |
DAF | Nonsense: hom or compound het | CHAPLE Syndrome; linked to Inab Cromer blood group |
CD59 | Nonsense: hom or compound het | CD59 deficiency; PNH-like disease; Peripheral neuropathy; strokes |
CFHR1/3 | Combined gene deletion | Risk for aHUS; protection from AMD |
CFHR5 | Gene duplication SNPs | aHUS C3G; poststreptococcal glomerulonephritis |
Clu | SNPs | AD |
CR1 | SNPs | AD |
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Torvell, M.; Carpanini, S.M.; Daskoulidou, N.; Byrne, R.A.J.; Sims, R.; Morgan, B.P. Genetic Insights into the Impact of Complement in Alzheimer’s Disease. Genes 2021, 12, 1990. https://0-doi-org.brum.beds.ac.uk/10.3390/genes12121990
Torvell M, Carpanini SM, Daskoulidou N, Byrne RAJ, Sims R, Morgan BP. Genetic Insights into the Impact of Complement in Alzheimer’s Disease. Genes. 2021; 12(12):1990. https://0-doi-org.brum.beds.ac.uk/10.3390/genes12121990
Chicago/Turabian StyleTorvell, Megan, Sarah M. Carpanini, Nikoleta Daskoulidou, Robert A. J. Byrne, Rebecca Sims, and B. Paul Morgan. 2021. "Genetic Insights into the Impact of Complement in Alzheimer’s Disease" Genes 12, no. 12: 1990. https://0-doi-org.brum.beds.ac.uk/10.3390/genes12121990