title: Effects of SORL1 gene on Alzheimer's disease. Focus on gender, neuropsychiatric symptoms and pro-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.
authors: Institute of Psychiatry, University of Bologna, Bologna, Italy.
authors: Paolo
authors: P
authors: Olgiati
authors: Antonis
authors: A
authors: Politis
authors: Diego
authors: D
authors: Albani
authors: Serena
authors: S
authors: Rodilossi
authors: Letizia
authors: L
authors: Polito
authors: Aikaterini
authors: A
authors: Zisaki
authors: Christina
authors: C
authors: Piperi
authors: Ioannis
authors: I
authors: Liappas
authors: Evangelia
authors: E
authors: Stamouli
authors: Antonis
authors: A
authors: Mailis
authors: Sara
authors: S
authors: Batelli
authors: Gianluigi
authors: G
authors: Forloni
authors: Agnese
authors: A
authors: Marsano
authors: Martina
authors: M
authors: Balestri
authors: Costantine R
authors: CR
authors: Soldatos
authors: Diana
authors: D
authors: De Ronchi
authors: Anastasios
authors: A
authors: Kalofoutis
authors: Alessandro
authors: A
authors: Serretti
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics / Q000276:immunology; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003072:Cognition Disorders / Q000209:etiology* / Q000235:genetics; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic / Q000235:genetics; D011569:Psychiatric Status Rating Scales; D012727:Sex Characteristics
chemical_list: D016207:Cytokines; D026502:LDL-Receptor Related Proteins; D026901:Membrane Transport Proteins; C102582:SORL1 protein, human