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