Dysregulated NF-κb pathway in peripheral mononuclear cells of alzheimer's disease patients

Arianna Ascolani, Emanuela Balestrieri, Antonella Minutolo, Serena Mosti, Gianfranco Spalletta, Placido Bramanti, Antonio Mastino, Carlo Caltagirone, Beatrice Macchi

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Diagnosis and therapeutic strategies in Alzheimer's disease (AD) might greatly benefit of the present multidisciplinary approach for studying the molecular pathogenesis of the disorder. Gene expression profile at peripheral level could be a promising tool for pathogenic studies as well as for early diagnosis of AD. A dysregulated inflammatory response, as well as other systemic disorders, have been described in AD. Therefore, we investigated the expression, at peripheral level, of a number of genes involved in the inflammatory, oxidative stress and proliferative response of a well defined, small cohort of sporadic AD patients. Firstly, the mRNA expression of inflammatory, stress and proliferation/differentiation genes were evaluated, using SuperArray, in mitogen-stimulated peripheral blood mononuclear cells (PBMC) from a group of 12 well-characterized, sporadic AD patients with various levels of dementia, by comparison with aged-matched controls. Real-time RT-PCR confirmed the trend of alteration in 16 genes out of the 36 supposed to be dysregulated in AD patients, by the preliminary screening. The expression level of the NFKB1(p105/50Kd) gene was significantly higher in AD with respect to adult age-matched controls (AA) and was related to the Mini-Mental State Examination (MMSE) score of the same patients. In addition, the expression of various NF-κB target genes and of both NF-κBp50 and NF-κBp65 DNA-binding activity were increased in PBMC from AD patients in comparison with those from AA. Our results suggest that NF-κ B activation at peripheral blood cell level could be a potential new hallmark of AD progression and sustain a rationale to more deeply investigate the therapeutic potential of specific NF-κB inhibitors in AD.

Original languageEnglish
Pages (from-to)128-137
Number of pages10
JournalCurrent Alzheimer Research
Volume9
Issue number1
DOIs
Publication statusPublished - Jan 2012

Fingerprint

Alzheimer Disease
Blood Cells
Genes
Mitogens
Transcriptome
Dementia
Disease Progression
Real-Time Polymerase Chain Reaction
Early Diagnosis
Oxidative Stress
Messenger RNA
DNA
Therapeutics

Keywords

  • Alzheimer's disease
  • Inflammation
  • Mmse
  • Nf-κb
  • Pbmcs
  • Superarray

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Dysregulated NF-κb pathway in peripheral mononuclear cells of alzheimer's disease patients. / Ascolani, Arianna; Balestrieri, Emanuela; Minutolo, Antonella; Mosti, Serena; Spalletta, Gianfranco; Bramanti, Placido; Mastino, Antonio; Caltagirone, Carlo; Macchi, Beatrice.

In: Current Alzheimer Research, Vol. 9, No. 1, 01.2012, p. 128-137.

Research output: Contribution to journalArticle

Ascolani, Arianna ; Balestrieri, Emanuela ; Minutolo, Antonella ; Mosti, Serena ; Spalletta, Gianfranco ; Bramanti, Placido ; Mastino, Antonio ; Caltagirone, Carlo ; Macchi, Beatrice. / Dysregulated NF-κb pathway in peripheral mononuclear cells of alzheimer's disease patients. In: Current Alzheimer Research. 2012 ; Vol. 9, No. 1. pp. 128-137.
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