Abstract
Pro-inflammatory cytokines and acute-phase proteins play an important role in Alzheimer's disease (AD) neurodegeneration, and common polymorphisms of genes controlling their production have been shown to be associated with AD. Tumor necrosis factor (TNF)-α is an inflammatory cytokine involved in the local immune response occurring in the central nervous system of AD patients. Genetic variation could contribute to the risk of developing AD or influence the age at the onset of the disease. We genotyped 222 patients (152 women, 70 men; age range 60-87) and 240 non-demented age-matched healthy controls for TNF-α -308 G/A single nucleotide polymorphism (SNP). No significant differences were observed in genotyped frequencies between patients and controls, whereas carriers of -308A showed a significantly lower mean age at onset than non-carriers of this allele. This difference was more evident taking into account ApolipoproteinE (ApoE) status since the lowest age at onset was observed in patients carrying the -308ATNF+/APOE4+ genotypes. In conclusion, our data support previous suggestions that, at least in Caucasians, the TNF gene is a disease modifier gene in patients in which AD is rising, bringing to light the importance of genetic variation at the pro-inflammatory components in the progression of AD.
| Original language | English |
|---|---|
| Pages (from-to) | 567-571 |
| Number of pages | 5 |
| Journal | Mechanisms of Ageing and Development |
| Volume | 127 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 2006 |
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Keywords
- Alzheimer's disease
- Cytokine
- Inflammation
- SNP
- TNF-α
ASJC Scopus subject areas
- Ageing
- Biochemistry
- Developmental Biology
- Developmental Neuroscience
Cite this
Tumor necrosis factor-α-308A/G polymorphism is associated with age at onset of Alzheimer's disease. / Lio, Domenico; Annoni, Giorgio; Licastro, Federico; Crivello, Antonino; Forte, Giusi Irma; Scola, Letizia; Colonna-Romano, Giuseppina; Candore, Giuseppina; Arosio, Beatrice; Galimberti, Lorenza; Vergani, Carlo; Caruso, Calogero.
In: Mechanisms of Ageing and Development, Vol. 127, No. 6, 06.2006, p. 567-571.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Tumor necrosis factor-α-308A/G polymorphism is associated with age at onset of Alzheimer's disease
AU - Lio, Domenico
AU - Annoni, Giorgio
AU - Licastro, Federico
AU - Crivello, Antonino
AU - Forte, Giusi Irma
AU - Scola, Letizia
AU - Colonna-Romano, Giuseppina
AU - Candore, Giuseppina
AU - Arosio, Beatrice
AU - Galimberti, Lorenza
AU - Vergani, Carlo
AU - Caruso, Calogero
PY - 2006/6
Y1 - 2006/6
N2 - Pro-inflammatory cytokines and acute-phase proteins play an important role in Alzheimer's disease (AD) neurodegeneration, and common polymorphisms of genes controlling their production have been shown to be associated with AD. Tumor necrosis factor (TNF)-α is an inflammatory cytokine involved in the local immune response occurring in the central nervous system of AD patients. Genetic variation could contribute to the risk of developing AD or influence the age at the onset of the disease. We genotyped 222 patients (152 women, 70 men; age range 60-87) and 240 non-demented age-matched healthy controls for TNF-α -308 G/A single nucleotide polymorphism (SNP). No significant differences were observed in genotyped frequencies between patients and controls, whereas carriers of -308A showed a significantly lower mean age at onset than non-carriers of this allele. This difference was more evident taking into account ApolipoproteinE (ApoE) status since the lowest age at onset was observed in patients carrying the -308ATNF+/APOE4+ genotypes. In conclusion, our data support previous suggestions that, at least in Caucasians, the TNF gene is a disease modifier gene in patients in which AD is rising, bringing to light the importance of genetic variation at the pro-inflammatory components in the progression of AD.
AB - Pro-inflammatory cytokines and acute-phase proteins play an important role in Alzheimer's disease (AD) neurodegeneration, and common polymorphisms of genes controlling their production have been shown to be associated with AD. Tumor necrosis factor (TNF)-α is an inflammatory cytokine involved in the local immune response occurring in the central nervous system of AD patients. Genetic variation could contribute to the risk of developing AD or influence the age at the onset of the disease. We genotyped 222 patients (152 women, 70 men; age range 60-87) and 240 non-demented age-matched healthy controls for TNF-α -308 G/A single nucleotide polymorphism (SNP). No significant differences were observed in genotyped frequencies between patients and controls, whereas carriers of -308A showed a significantly lower mean age at onset than non-carriers of this allele. This difference was more evident taking into account ApolipoproteinE (ApoE) status since the lowest age at onset was observed in patients carrying the -308ATNF+/APOE4+ genotypes. In conclusion, our data support previous suggestions that, at least in Caucasians, the TNF gene is a disease modifier gene in patients in which AD is rising, bringing to light the importance of genetic variation at the pro-inflammatory components in the progression of AD.
KW - Alzheimer's disease
KW - Cytokine
KW - Inflammation
KW - SNP
KW - TNF-α
UR - http://www.scopus.com/inward/record.url?scp=33646147149&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33646147149&partnerID=8YFLogxK
U2 - 10.1016/j.mad.2006.01.015
DO - 10.1016/j.mad.2006.01.015
M3 - Article
VL - 127
SP - 567
EP - 571
JO - Mechanisms of Ageing and Development
JF - Mechanisms of Ageing and Development
SN - 0047-6374
IS - 6
ER -