Journal of Neurology

, Volume 250, Issue 6, pp 688–692 | Cite as

The 129 codon polymorphism of the Prion Protein gene influences earlier cognitive performance in Down syndrome subjects

  • Roberto Del Bo
  • Giacomo Pietro Comi
  • Roberto Giorda
  • Marco Crimi
  • Federica Locatelli
  • Filippo Martinelli-Boneschi
  • Uberto Pozzoli
  • Enrico Castelli
  • Nereo Bresolin
  • Guglielmo Scarlato
ORIGINAL COMMUNICATION

Abstract.

Recently, a frequent prion protein gene (PRNP) polymorphism consisting of a methionine (M) for valine (V) substitution at codon 129 has been associated with cognitive impairment in elderly individuals. Down syndrome (DS) is associated with mental retardation and development of Alzheimer-like brain abnormalities. In the present study, we investigated the role of the PRNP polymorphism in 122 relatively young Italian DS patients. Allele frequencies of DS subjects did not differ from those in the general population. However, we found a significantly faster rate of decline in intellectual ability in the subgroup of DS patients carrying at least one V allele compared with the M/M DS subjects. An additive deleterious effect of apolipoprotein E ɛ4 allele was detected after stratifying by APOE gene status. Our findings provide evidence that variability of the PRNP gene at codon 129 might contribute to accelerating the rate of earlier cognitive decline in DS subjects.

Key words Down syndrome prion protein apolipoprotein E mental retardation Alzheimer's disease 

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Copyright information

© Steinkopff Verlag 2003

Authors and Affiliations

  • Roberto Del Bo
    • 1
  • Giacomo Pietro Comi
    • 1
  • Roberto Giorda
    • 2
  • Marco Crimi
    • 1
  • Federica Locatelli
    • 1
  • Filippo Martinelli-Boneschi
    • 1
  • Uberto Pozzoli
    • 2
  • Enrico Castelli
    • 2
  • Nereo Bresolin
    • 1
  • Guglielmo Scarlato
    • 1
  1. 1.Dipartimento di Scienze Neurologiche, Padiglione Ponti, I. R. C. S. S. Ospedale Maggiore Policlinico, Via F. Sforza, 35, 20122 Milan, Italy. gpcomi@mailserver.unimi.itIT
  2. 2.I. R. C. C. S. “E. Medea” de La Nostra Famiglia, Bosisio Parini, ItalyIT
  3. 3.Centre of Excellence on Neurodegenerative Diseases, University of Milan, Milan, ItalyIT

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