Effects of SORL1 Gene on Alzheimer's Disease. Focus on Gender, Neuropsychiatric Symptoms and Pro-Inflammatory Cytokines

Title:Effects of SORL1 Gene on Alzheimer's Disease. Focus on Gender, Neuropsychiatric Symptoms and Pro-Inflammatory Cytokines

Volume: 10 Issue: 2

Author(s): Antonis Mailis, Alessandro Serretti, Anastasios Kalofoutis, Diana De Ronchi, Costantine R.Soldatos, Martina Balestri, Agnese Marsano, Gianluigi Forloni, Sara Batelli, Paolo Olgiati, Evangelia Stamouli, Ioannis Liappas, Christina Piperi, Aikaterini Zisaki, Letizia Polito, Serena Rodilossi, Diego Albani and Antonis Politis

Affiliation:

Keywords: SORL1, gender, Alzheimer, psychosis, inflammatory cytokines

Abstract: It was suggested that the gene encoding for sorLa, (SORL1) may affect Alzheimer's disease (LOAD) through a female-specific mechanism. The aims of this study were to confirm the role of gender in modulating the association between SORL1 and LOAD and to ascertain the influence of SORL1 on cognitive impairment, neuropsychiatric symptoms (BPSD) and secretion of pro-inflammatory cytokines.

Ninety six outpatients with LOAD and 120 unrelated controls were genotyped for APOE and three SNPs at the 5' end of SORL1(intron 6): SNP 8 (rs668387); SNP 9 (rs68902); SNP 10 (rs641120). Clinical evaluation was made with the MMSE, Neuropsychiatric Inventory (NPI) and Cornell Scale for Depression in Dementia (CDDS). ELISPOT assays were used to measure pro-inflammatory cytokine (TNF-alpha; IL-6; IL-1beta; IFN-gamma) production in peripheral blood mononuclear cell (PBMC) supernatant from AD patients.

SORL1 SNPs were not associated with LOAD in overall sample. Instead the G-alleles at SNPs 9 (p=0.015) and 10 (p=0.015) and the CGG haplotype (p=0.02) were associated with LOAD in the women subgroup. The TAA haplotype was marginally protective in AD patients being associated with lower BPSD scores (p=0.01). The same haplotype was also associated with higher IL-1beta (p=0.01) production. These genetic effects were not modified by APOE4 allele and controlled for illness duration and treatment.

In conclusion, SORL1 does not appear to be a major risk factor for LOAD. Its contribution could be underestimated in our small sample. Sex-specific factors could modulate the association between SORL1 and AD. The influence of SORL1 variants on production of inflammatory cytokines warrants further investigation.

Cite this article as:

Mailis Antonis, Serretti Alessandro, Kalofoutis Anastasios, De Ronchi Diana, R.Soldatos Costantine, Balestri Martina, Marsano Agnese, Forloni Gianluigi, Batelli Sara, Olgiati Paolo, Stamouli Evangelia, Liappas Ioannis, Piperi Christina, Zisaki Aikaterini, Polito Letizia, Rodilossi Serena, Albani Diego and Politis Antonis, Effects of SORL1 Gene on Alzheimer's Disease. Focus on Gender, Neuropsychiatric Symptoms and Pro-Inflammatory Cytokines, Current Alzheimer Research 2013; 10 (2) . https://dx.doi.org/10.2174/1567205011310020005

DOI https://dx.doi.org/10.2174/1567205011310020005	Print ISSN 1567-2050
Publisher Name Bentham Science Publisher	Online ISSN 1875-5828