The 129 codon polymorphism of the prion protein gene influences earlier cognitive performance in Down syndrome subjects

Topic: Brain proteins, microglia and lab models

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.

Key findings

• 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.
• 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.
• 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.

Why it matters

Among 122 relatively young people with Down syndrome, those carrying at least one valine allele of the PRNP codon 129 polymorphism showed a faster decline in intellectual ability. This describes a genetic influence on cognitive decline and does not test any treatment, cure, or prevention.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1007/s00415-003-1057-5
• PubMed: 12796830
• Original source →

May need a subscription OpenAlex found no free copy of the full text (checked 6 Feb 1020), so the publisher may charge for it. The PubMed abstract is free.

@article{delbo2003-12796830,
  author  = {Del Bo, R. and Comi, G. P. and Giorda, R. and Crimi, M. and Locatelli, F. and Martinelli-Boneschi, F. and Pozzoli, U. and Castelli, E. and others},
  title   = {{The 129 codon polymorphism of the prion protein gene influences earlier cognitive performance in Down syndrome subjects}},
  journal = {Journal of neurology},
  year    = {2003},
  doi     = {10.1007/s00415-003-1057-5},
  pmid    = {12796830},
  url     = {https://doi.org/10.1007/s00415-003-1057-5}
}

Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• APOE genotype and gender effects on Alzheimer disease in 100 adults with Down syndrome Neurology · 1999-07-01 · usefulness score 55/100 · Genetics
• Presenilin 1 and alpha-1-antichymotrypsin polymorphisms in Down syndrome: no effect on the presence of dementia American journal of medical genetics · 1999-12-01 · usefulness score 39/100 · Down syndrome and Alzheimer's
• Allele varepsilon4 of apolipoprotein E gene is less frequent in Down syndrome patient of the Sicilian population and has no influence on the grade of mental retardation Neuroscience letters · 2001-06-01 · usefulness score 36/100 · Down syndrome and Alzheimer's

Later studies that cite this one

3 studies in the alzhub library list this one in their references.

• Alzheimer disease and Down syndrome: factors in pathogenesis Neurobiology of aging · 2005-03-01 · usefulness score 43/100 · Down syndrome and Alzheimer's
• Down syndrome, Alzheimer's disease and seizures Brain & development · 2005-06-01 · usefulness score 40/100 · Down syndrome and Alzheimer's
• High capacity and low cost detection of prion protein gene variant alleles by denaturing HPLC Journal of neuroscience methods · 2004-10-01 · usefulness score 31/100 · Down syndrome and Alzheimer's

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• Association between presenilin-1 polymorphism and maternal meiosis II errors in Down syndrome American journal of medical genetics · 2000-08-01 · usefulness score 41/100
• Mapping of the gene encoding the beta-amyloid precursor protein and its relationship to the Down syndrome region of chromosome 21 Proceedings of the National Academy of Sciences of the United States of America · 1988-11-01 · usefulness score 44/100
• Feasibility of Lumbar Puncture in the Study of Cerebrospinal Fluid Biomarkers for Alzheimer's Disease in Subjects with Down Syndrome Journal of Alzheimer's disease : JAD · 2017-01-01 · usefulness score 45/100
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