Expression of the transcription factor Sp1 and its regulatory hsa-miR-29b in peripheral blood mononuclear cells from patients with alzheimer's disease

Chiara Villa, Elisa Ridolfi, Chiara Fenoglio, Laura Ghezzi, Roberto Vimercati, Francesca Clerici, Alessandra Marcone, Salvatore Gallone, Maria Serpente, Claudia Cantoni, Rossana Bonsi, Sara Cioffi, Stefano Cappa, Massimo Franceschi, Innocenzo Rainero, Claudio Mariani, Elio Scarpini, Daniela Galimberti

Research output: Contribution to journalArticlepeer-review

Abstract

Altered gene expression occurs in central nervous system disorders, including Alzheimer's disease (AD). Transcription factor Sp1 (specificity protein 1) can regulate the expression of several AD-related proteins, including amyloid-β protein precursor and tau. Sp1 is regulated by oxidative stress, and Sp1 mRNA was found to be upregulated in AD cortex and hippocampus. The distribution of three single nucleotide polymorphisms (SNPs), including rs7300593, rs17695156, and rs12821290, covering 100% Sp1 genetic variability, has been determined in a population of 393 AD patients as compared with 412 controls. In addition, expression analysis of Sp1 and its regulatory microRNAs (hsa-miR-29b and hsa-miR-375) has been performed in peripheral blood mononuclear cells (PBMCs), together with Sp1 protein analysis. No differences in all three SNP distributions were observed in AD patients as compared with controls. Stratifying according to gender, a significantly decreased frequency of Sp1 rs17695156 T allele was observed in male patients versus male controls. Significantly increased Sp1 relative expression levels were observed in PBMCs from AD patients as compared with controls. Western blot analysis paralleled mRNA increase in AD patients versus controls and correlated positively with Sp1 mRNA levels. Significantly decreased relative expression levels of hsa-miR-29b, but not of hsa-miR-375, were observed in AD patients versus controls and correlated negatively with Sp1 mRNA levels. According to these results, Sp1 and its regulatory hsa-miR-29b are deregulated in AD patients, possibly leading to aberrant production of downstream target genes involved in the pathogenesis. Moreover, Sp1 rs176951056 T allele is likely a protective factor in the male population.

Original languageEnglish
Pages (from-to)487-494
Number of pages8
JournalJournal of Alzheimer's Disease
Volume35
Issue number3
DOIs
Publication statusPublished - 2013

Keywords

  • Alzheimer's disease
  • expression
  • gene regulation
  • microRNAs
  • peripheral blood mononuclear cells
  • risk factor
  • Sp1

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology

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