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.
Background: Neurofibrillary tangles and senile plaques are hallmarks of Alzheimer’s disease (AD) although the molecular basis of their coexistence remains elusive. The peptidyl-prolyl cis/trans isomerase Pin1 acts on both tau and amyloid precursor protein to regulate their functions by influencing tau phosphorylation and amyloid precursor protein processing. Objective: In order to identify potential biomarkers for AD in easily accessible cells and to gain insight into the relationship between the brain and peripheral compartments in AD pathology, we investigated Pin1 expression and activity in the peripheral blood mononuclear cells of subjects with late-onset AD (LOAD) and age-matched controls (CT). Methods: Gene and protein expression, promoter methylation, Ser16 phosphorylation and activity of Pin1 were evaluated in 32 samples from subjects with LOAD and in 28 samples from CT. Results: In LOAD subjects, there was a statistically significant reduction in Ser16 phosphorylation (–30%; p = 0.041) and promoter methylation (–8%; p = 0.001), whereas Pin1 expression was significantly increased (+74%; p = 0.018). Conclusion: The modifications of Pin1 found in LOAD subjects support its involvement in the pathogenesis of the disease with an important role being played by epigenetic mechanisms.
Adenosine suppresses immune responses through the adenosine A2A receptors (A2AR). We evaluated the expression of A2AR in blood mononuclear cells (PBMCs) of patients with mild cognitive impairment (MCI), Alzheimer's disease (AD), and controls in order to verify if it may help distinguish different forms of cognitive decline. There was a significant linear increase in both mRNA levels and receptor density from multiple cognitive domain MCI (mcd-MCI) to amnestic MCI (a-MCI), spanning through AD and controls, without any significant difference between the latter two groups of subjects. These data, which need to be confirmed in a larger number of patients, suggest that expression of A2AR in PBMCs may be a valuable means of differentiating a-MCI and mcd-MCI.
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