Abstract
Tumor necrosis factor (TNF), a proinflammatory cytokine, may be involved in the pathogenesis of Alzheimer disease (AD) based on observations that senile plaques have been found to upregulate proinflammatory cytokines. Additionally, nonsteroidal anti-inflammatory drugs have been found to delay and prevent the onset of AD. A collaborative genome-wide scan for AD genes in 266 late-onset families implicated a 20 centimorgan region at chromosome 6p21.3 that includes the TNF gene. Three TNF polymorphisms, a -308 TNF promoter polymorphism, whose TNF2 allele is associated with autoimmune inflammatory diseases and strong transcriptional activity, the -238 TNF promoter polymorphism, and the microsatellite TNFa, whose 2 allele is associated with a high TNF secretion, were typed in 145 families consisting of 562 afleered and unaffected siblings. These polymorphisms formed a haplotype, 2-1-2, re-spectively, that was significantly associated with AD (P = 0.005) using the sibling disequilibrium test. Singly, the TNFa2 allele was also significantly associated (P = 0.04) with AD in these 145 families. This TNF association with AD lends further support for an inflammatory process in the pathogenesis of AD. (C) 2000 Wiley-Liss, Inc.
Original language | English (US) |
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Pages (from-to) | 823-830 |
Number of pages | 8 |
Journal | American Journal of Medical Genetics - Neuropsychiatric Genetics |
Volume | 96 |
Issue number | 6 |
DOIs | |
State | Published - Dec 4 2000 |
Keywords
- Chromosome 6
- Cytokine
- Dementia
- HLA
- TNF
ASJC Scopus subject areas
- Genetics(clinical)
- Psychiatry and Mental health
- Cellular and Molecular Neuroscience