Effects of SORL1 gene on Alzheimer's disease. focus on gender, neuropsychiatric symptoms and pro-inflammatory cytokines

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)154-164
Number of pages11
JournalCurrent Alzheimer Research
Volume10
Issue number2
DOIs
StatePublished - 2013
Externally publishedYes

Fingerprint

Single Nucleotide Polymorphism
Alzheimer Disease
Cytokines
Haplotypes
Genes
Alleles
Enzyme-Linked Immunospot Assay
Sex Factors
Introns
Dementia
Interleukin-6
Blood Cells
Outpatients
Tumor Necrosis Factor-alpha
Depression
Equipment and Supplies

Keywords

  • Alzheimer
  • Gender
  • Inflammatory cytokines
  • Psychosis
  • SORL1

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Effects of SORL1 gene on Alzheimer's disease. focus on gender, neuropsychiatric symptoms and pro-inflammatory cytokines. / Olgiati, Paolo; Politis, Antonis; Albani, Diego; Rodilossi, Serena; Polito, Letizia; Zisaki, Aikaterini; Piperi, Christina; Liappas, Ioannis; Stamouli, Evangelia; Mailis, Antonis; Batelli, Sara; Forloni, Gianluigi; Marsano, Agnese; Balestri, Martina; Soldatos, Costantine R.; de Ronchi, Diana; Kalofoutis, Anastasios; Serretti, Alessandro.

In: Current Alzheimer Research, Vol. 10, No. 2, 2013, p. 154-164.

Research output: Contribution to journalArticle

Olgiati, P, Politis, A, Albani, D, Rodilossi, S, Polito, L, Zisaki, A, Piperi, C, Liappas, I, Stamouli, E, Mailis, A, Batelli, S, Forloni, G, Marsano, A, Balestri, M, Soldatos, CR, de Ronchi, D, Kalofoutis, A & Serretti, A 2013, 'Effects of SORL1 gene on Alzheimer's disease. focus on gender, neuropsychiatric symptoms and pro-inflammatory cytokines', Current Alzheimer Research, vol. 10, no. 2, pp. 154-164. https://doi.org/10.2174/1567205011310020005
Olgiati, Paolo ; Politis, Antonis ; Albani, Diego ; Rodilossi, Serena ; Polito, Letizia ; Zisaki, Aikaterini ; Piperi, Christina ; Liappas, Ioannis ; Stamouli, Evangelia ; Mailis, Antonis ; Batelli, Sara ; Forloni, Gianluigi ; Marsano, Agnese ; Balestri, Martina ; Soldatos, Costantine R. ; de Ronchi, Diana ; Kalofoutis, Anastasios ; Serretti, Alessandro. / Effects of SORL1 gene on Alzheimer's disease. focus on gender, neuropsychiatric symptoms and pro-inflammatory cytokines. In: Current Alzheimer Research. 2013 ; Vol. 10, No. 2. pp. 154-164.
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AU - Rodilossi, Serena

AU - Polito, Letizia

AU - Zisaki, Aikaterini

AU - Piperi, Christina

AU - Liappas, Ioannis

AU - Stamouli, Evangelia

AU - Mailis, Antonis

AU - Batelli, Sara

AU - Forloni, Gianluigi

AU - Marsano, Agnese

AU - Balestri, Martina

AU - Soldatos, Costantine R.

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