Journal of Neurology

, Volume 250, Issue 6, pp 688–692

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

Authors

  • Roberto Del Bo
    • Dipartimento di Scienze Neurologiche, Padiglione Ponti, I. R. C. S. S. Ospedale Maggiore Policlinico, Via F. Sforza, 35, 20122 Milan, Italy. gpcomi@mailserver.unimi.it
  • Giacomo Pietro Comi
    • Dipartimento di Scienze Neurologiche, Padiglione Ponti, I. R. C. S. S. Ospedale Maggiore Policlinico, Via F. Sforza, 35, 20122 Milan, Italy. gpcomi@mailserver.unimi.it
  • Roberto Giorda
    • I. R. C. C. S. “E. Medea” de La Nostra Famiglia, Bosisio Parini, Italy
  • Marco Crimi
    • Dipartimento di Scienze Neurologiche, Padiglione Ponti, I. R. C. S. S. Ospedale Maggiore Policlinico, Via F. Sforza, 35, 20122 Milan, Italy. gpcomi@mailserver.unimi.it
  • Federica Locatelli
    • Dipartimento di Scienze Neurologiche, Padiglione Ponti, I. R. C. S. S. Ospedale Maggiore Policlinico, Via F. Sforza, 35, 20122 Milan, Italy. gpcomi@mailserver.unimi.it
  • Filippo Martinelli-Boneschi
    • Dipartimento di Scienze Neurologiche, Padiglione Ponti, I. R. C. S. S. Ospedale Maggiore Policlinico, Via F. Sforza, 35, 20122 Milan, Italy. gpcomi@mailserver.unimi.it
  • Uberto Pozzoli
    • I. R. C. C. S. “E. Medea” de La Nostra Famiglia, Bosisio Parini, Italy
  • Enrico Castelli
    • I. R. C. C. S. “E. Medea” de La Nostra Famiglia, Bosisio Parini, Italy
  • Nereo Bresolin
    • Dipartimento di Scienze Neurologiche, Padiglione Ponti, I. R. C. S. S. Ospedale Maggiore Policlinico, Via F. Sforza, 35, 20122 Milan, Italy. gpcomi@mailserver.unimi.it
  • Guglielmo Scarlato
    • Dipartimento di Scienze Neurologiche, Padiglione Ponti, I. R. C. S. S. Ospedale Maggiore Policlinico, Via F. Sforza, 35, 20122 Milan, Italy. gpcomi@mailserver.unimi.it
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DOI: 10.1007/s00415-003-1057-5

Cite this article as:
Del Bo, R., Comi, G., Giorda, R. et al. J Neurol (2003) 250: 688. doi:10.1007/s00415-003-1057-5

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 syndromeprion proteinapolipoprotein Emental retardationAlzheimer's disease
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© Steinkopff Verlag 2003