Pin1 contribution to Alzheimer's disease: Transcriptional and epigenetic mechanisms in patients with late-onset Alzheimer's disease

B. Arosio, A. Bulbarelli, S. Bastias Candia, E. Lonati, L. Mastronardi, P. Romualdi, S. Candeletti, C. Gussago, D. Galimberti, E. Scarpini, B. Dell'Osso, C. Altamura, M. MacCarrone, L. Bergamaschini, C. D'Addario, D. Mari

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Neurofibrillary tangles and senile plaques are hallmarks of Alzheimer's disease (AD) although the molecular basis of their coexistence remains elusive. The peptidyl-prolyl cis/trans isomerase Pin1 acts on both tau and amyloid precursor protein to regulate their functions by influencing tau phosphorylation and amyloid precursor protein processing. Objective: In order to identify potential biomarkers for AD in easily accessible cells and to gain insight into the relationship between the brain and peripheral compartments in AD pathology, we investigated Pin1 expression and activity in the peripheral blood mononuclear cells of subjects with late-onset AD (LOAD) and age-matched controls (CT). Methods: Gene and protein expression, promoter methylation, Ser 16 phosphorylation and activity of Pin1 were evaluated in 32 samples from subjects with LOAD and in 28 samples from CT. Results: In LOAD subjects, there was a statistically significant reduction in Ser 16 phosphorylation (-30%; p = 0.041) and promoter methylation (-8%; p = 0.001), whereas Pin1 expression was significantly increased (+74%; p = 0.018). Conclusion: The modifications of Pin1 found in LOAD subjects support its involvement in the pathogenesis of the disease with an important role being played by epigenetic mechanisms.

Original languageEnglish
Pages (from-to)207-211
Number of pages5
JournalNeurodegenerative Diseases
Volume10
Issue number1-4
DOIs
Publication statusPublished - Apr 2012

Keywords

  • Alzheimer's disease
  • Epigenetic mechanisms
  • Phosphorylation mechanisms
  • Pin1

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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