title: The 129 codon polymorphism of the prion protein gene influences earlier cognitive performance in Down syndrome subjects.
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 epsilon 4 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.
authors.affiliation: 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
authors.forename: Roberto
authors.initials: R
authors.lastname: Del Bo
authors.forename: Giacomo Pietro
authors.initials: GP
authors.lastname: Comi
authors.forename: Roberto
authors.initials: R
authors.lastname: Giorda
authors.forename: Marco
authors.initials: M
authors.lastname: Crimi
authors.forename: Federica
authors.initials: F
authors.lastname: Locatelli
authors.forename: Filippo
authors.initials: F
authors.lastname: Martinelli-Boneschi
authors.forename: Uberto
authors.initials: U
authors.lastname: Pozzoli
authors.forename: Enrico
authors.initials: E
authors.lastname: Castelli
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: Guglielmo
authors.initials: G
authors.lastname: Scarlato
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000483:Alleles; D019943:Amino Acid Substitution; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000145:classification / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003062:Codon; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics*; D004314:Down Syndrome / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007361:Intelligence Tests; D008297:Male; D008715:Methionine / Q000235:genetics; D009154:Mutation; D011110:Polymorphism, Genetic; D011328:Prions / Q000235:genetics*; D014633:Valine / Q000235:genetics
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D003062:Codon; D011328:Prions; D008715:Methionine; D014633:Valine