L’infiammazione nella malattia di Alzheimer: la genetica come fattore di rischio

Alzheimer’s disease is a neurodegenerative disorder determined by both genetic and environmental factors. In the last decade, thanks to epidemiological, post-mortem and experimental studies, the evidence was proven that the neuroinflammatory process contributes consistently in determining neuronal loss; later studies analyzed the polymorphisms of genes involved in the regulation of the inflammatory response searching for a genetic profile of susceptibility towards the disease. In our study we considered two polymorphisms of the RAGE gene (-374 T/A and -429 T/C) and three polymorphisms of the TNF-α gene (-857, -308 and -238 G/A), as both these molecules are strongly involved in the pathogenesis of the disease. We recruited 33 patients affected with cognitive deterioration (22 AD, 8 VaD, 3 MCI) from C. Mondino Foundation and 220 healthy controls comparable for sex, age and rage to the population of interest. The purpose of our research was first to determine whether any of the polymorphisms increased individual susceptibility towards the disease, and second to verify if these polymorphisms correlated with some chosen clinical (age of onset and rate of progression, evaluated with MMSE score) and inflammatory parameters (CRP and PINI). The comparison of the allelic and genotypic frequencies in the population of affected and healthy controls showed that the AG genotype of -238 G/A polymorphism of TNF-α gene was significantly more frequent among the affected (genotypic freq. χ²=0.013; allelic freq. χ²=0.046). Then, as RAGE and TNF-α genes are both localized on chromosome 6 in the HLA III region, we compared the haplotypic frequencies resulting from the combination of the five polymorphisms in the group of affected and in the group of controls and we found that the TTGAA haplotype was significantly less frequent among the affected (p-value=0.018). No statistically significant correlation between the polymorphisms and the clinical (age of onset and rate of progression) and inflammatory parameters (CRP and PINI) was found.