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Aging Clinical and Experimental Research

, Volume 19, Issue 5, pp 406–409 | Cite as

PIN-1 promoter polymorphisms in mild cognitive impairment and susceptibility to Alzheimer’s disease: a preliminary report

  • Beatrice ArosioEmail author
  • Ludovica Segat
  • Michele Milanese
  • Lorenza Galimberti
  • Carmen Calabresi
  • Mariella Zanetti
  • Daria Trabattoni
  • Giorgio Annoni
  • Sergio Crovella
  • Carlo Vergani
Original Articles

Abstract

Background and aims: Peptydil prolyl cis-trans isomerase (PIN-1), which specifically regulates the conformational changes following phosphorylation of several proteins, targets the inactive hyperphosphorylated tau on the Thr231-Pro motif and directly restores its biological function. Interestingly, PIN-1 is oxidatively inhibited not only in Alzheimer’s disease brain but also in the hippocampi of mild cognitive impairment (MCI) subjects. The PIN-1 gene is characterized by two single nucleotide polymorphisms (SNPs) in the promoter region which are associated with the risk of Alzheimer’s disease. The aim of this study was to analyse the genotype and allele distributions of these PIN-1 SNPs in MCI subjects diagnosed respectively as amnestic MCI (a-MCI) and multiple impaired cognitive domains (mcd-MCI) on the basis of cognitive features. Methods: −667 T/C and −842 C/G SNPs were genotyped by polymerase chain reaction (PCR) amplification and direct sequencing in 43 MCI subjects, with the intention of comparing −667 and −842 SNP frequencies with those previously described in 111 Alzheimer’s disease patients (AD) and 73 healthy controls (HC). Results: The allele frequencies of the −842 C/G SNP in a-MCI subjects are similar to those of AD subjects, while those of mcd-MCI are comparable to HC (G allele 83% in both a-MCI and AD; 95% and 94% in mcd-MCI and HC, respectively). A similar trend is also observed in −842 C/G genotypes. Conclusions: Since a-MCI is thought to be the preclinical form of AD, the similar genotype distribution of −842 SNP in AD and a-MCI, but not in mcd-MCI, suggests that it is potentially involved in the conversion of a-MCI to AD. In conclusion, these findings support the theory that polymorphisms of the PIN-1 gene can affect neurodegeneration and its clinical progression.

Keywords

Alzheimer’s disease genetic polymorphisms MCI PIN-1 

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Copyright information

© Springer Internal Publishing Switzerland 2007

Authors and Affiliations

  • Beatrice Arosio
    • 1
    Email author
  • Ludovica Segat
    • 2
  • Michele Milanese
    • 2
  • Lorenza Galimberti
    • 1
  • Carmen Calabresi
    • 1
  • Mariella Zanetti
    • 1
  • Daria Trabattoni
    • 4
  • Giorgio Annoni
    • 5
  • Sergio Crovella
    • 2
    • 3
  • Carlo Vergani
    • 1
  1. 1.Geriatric Unit, Department of Internal MedicineUniversity of Milano, Ospedale Maggiore Policlinico, IRCCS MilanoItaly
  2. 2.Department of Reproductive and Developmental SciencesUniversity of TriesteTrieste
  3. 3.Genetic Service, IRCCS Burlo GarofoloTrieste
  4. 4.DISP LITA VIALBA, University of MilanoMilano
  5. 5.DIMEP, University of Milano-BicoccaMilanoItaly

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