title: Pin1 contribution to Alzheimer's disease: transcriptional and epigenetic mechanisms in patients with late-onset Alzheimer's disease.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Geriatric Unit, University of Milan, Milan, Italy. beatrice.arosio @ unimi.it
authors.forename: B
authors.initials: B
authors.lastname: Arosio
authors.forename: A
authors.initials: A
authors.lastname: Bulbarelli
authors.forename: S
authors.initials: S
authors.lastname: Bastias Candia
authors.forename: E
authors.initials: E
authors.lastname: Lonati
authors.forename: L
authors.initials: L
authors.lastname: Mastronardi
authors.forename: P
authors.initials: P
authors.lastname: Romualdi
authors.forename: S
authors.initials: S
authors.lastname: Candeletti
authors.forename: C
authors.initials: C
authors.lastname: Gussago
authors.forename: D
authors.initials: D
authors.lastname: Galimberti
authors.forename: E
authors.initials: E
authors.lastname: Scarpini
authors.forename: B
authors.initials: B
authors.lastname: Dell'Osso
authors.forename: C
authors.initials: C
authors.lastname: Altamura
authors.forename: M
authors.initials: M
authors.lastname: MacCarrone
authors.forename: L
authors.initials: L
authors.lastname: Bergamaschini
authors.forename: C
authors.initials: C
authors.lastname: D'Addario
authors.forename: D
authors.initials: D
authors.lastname: Mari
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D000704:Analysis of Variance; D053327:Apolipoprotein E4 / Q000235:genetics; D016022:Case-Control Studies; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007558:Italy; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008745:Methylation; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000235:genetics* / Q000378:metabolism*; D010766:Phosphorylation / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012694:Serine / Q000378:metabolism
chemical_list: D053327:Apolipoprotein E4; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D012694:Serine; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase