Intereleukin-10 Promoter Polymorphism in Mild Cognitive Impairment and in Its Clinical Evolution

Beatrice Arosio,Carlo Vergani,Giorgio Annoni,Luigina Mastronardi

doi:10.4061/2010/854527

Abstract

Specific proinflammatory alleles are associated with higher risk of Alzheimer disease (AD) in different onset age. The homozygosis for the A allele of −1082 polymorphism (G/A) of interleukin-10 (IL-10) promotes a higher risk of AD and reduced IL-10 generation in peripheral cells after amyloid stimulation. In this paper we analysed genotype and allele frequencies of this polymorphism in 138 subjects with mild cognitive impairment (MCI) diagnosed, respectively, as amnestic (a-MCI) and multiple impaired cognitive domains (mcd-MCI). The genotype frequencies were similar in a-MCI and AD subjects, whereas in mcd-MCI comparable to controls (AA genotype: 50% in a-MCI, 49.2% in AD, 28.7% in mcd-MCI and 31.8% in controls). Consequently, both allele and genotype distributions were significantly different between a-MCI and mcd-MCI (allele: P = .02, genotype: P < .05). These results support the theory that polymorphisms of cytokine genes can affect neurodegeneration and its clinical progression. IL-10 may partly explain the conversion of a-MCI to AD or be a genetic marker of susceptibility.

Highlights

The pathogenic process of Alzheimer’s disease (AD) starts decades before the clinical onset of the disease [1]
We found that the homozygosis for the A allele of the IL-10 −1082 G/A single nucleotide polymorphism (SNP) was associated with six-fold higher risk of Alzheimer disease (AD)
It is interesting to note that the genotype frequencies of the −1082 SNP in a-mild cognitive impairment (MCI) subjects were similar to those of AD subjects, whereas those of mcd-MCI were comparable to healthy controls (HCs) (AA genotype 50% in amnestic MCI (a-MCI) and 49.2% in AD; 28.7% and 31.8% in mcd-MCI and HC, resp.) (Table 2)

Summary

Introduction

The pathogenic process of Alzheimer’s disease (AD) starts decades before the clinical onset of the disease [1]. During this preclinical phase, there is a gradual loss of axons and neurons, and at a certain threshold the first symptoms, most often impaired episodic memory, appear. There is a gradual loss of axons and neurons, and at a certain threshold the first symptoms, most often impaired episodic memory, appear At this stage, patients do not fulfil the criteria for dementia and may be diagnosed with mild cognitive impairment (MCI). An increased intrathecal production of the proinflammatory cytokine TNF-α and a decreased production of the antiinflammatory cytokine TGF-β have been demonstrated in the brain of patients with MCI, suggesting there is a proinflammatory state in such patients at high risk for AD [9]

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