Presenilin 1 and alpha-1-antichymotrypsin polymorphisms in Down syndrome: no effect on the presence of dementia

Topic: Brain proteins, microglia and lab models

As people with Down syndrome (DS) age, they are at greater risk for Alzheimer disease (AD) than the general population. It has been suggested that polymorphisms at the genes for presenilin-1 (PS-1) and alpha-1-antichymotrypsin (ACT) confer an increased risk for AD in the general population, and therefore potentially to AD in people with DS. We obtained DNA from 231 individuals with DS and 233 population controls. People with DS were evaluated for dementia. Allele frequencies at PS-1 and ACT polymorphisms in people with DS were compared to those in age-matched controls. There were no frequency differences between the control sample and DS sample for PS-1 or ACT alleles or genotypes. Similarly, there were no differences in allele frequencies between the demented and age-matched non-demented DS samples. However a higher frequency of PS-1 heterozygotes in the demented DS group was noted. We conclude that unlike the general population, neither PS-1 nor ACT polymorphisms appear to have a similar detrimental effect on dementia in DS. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:616-620, 1999.

@article{tyrrell1999-10581479,
  author  = {Tyrrell, J. and Cosgrave, M. and McPherson, J. and Hawi, Z. and Trulock, V. and Calvert, J. and Lawlor, B. and Gill, M.},
  title   = {{Presenilin 1 and alpha-1-antichymotrypsin polymorphisms in Down syndrome: no effect on the presence of dementia}},
  journal = {American journal of medical genetics},
  year    = {1999},
  doi     = {10.1002/(sici)1096-8628(19991215)88:6<616::aid-ajmg8>3.0.co;2-i},
  pmid    = {10581479},
  url     = {https://doi.org/10.1002/(sici)1096-8628(19991215)88:6<616::aid-ajmg8>3.0.co;2-i}
}

Key findings

• It has been suggested that polymorphisms at the genes for presenilin-1 (PS-1) and alpha-1-antichymotrypsin (ACT) confer an increased risk for AD in the general population, and therefore potentially to AD in people with DS.
• Allele frequencies at PS-1 and ACT polymorphisms in people with DS were compared to those in age-matched controls.
• We conclude that unlike the general population, neither PS-1 nor ACT polymorphisms appear to have a similar detrimental effect on dementia in DS.

Why it matters

In 231 people with Down syndrome, neither presenilin-1 nor alpha-1-antichymotrypsin polymorphisms appeared to increase the risk of dementia, unlike what has been suggested in the general population. A higher frequency of PS-1 heterozygotes was noted in the demented group, but the authors conclude these variants do not have a similar detrimental effect in Down syndrome.

Study details

• Participants231
• Evidence strengthLow

Read the original

• DOI: 10.1002/(sici)1096-8628(19991215)88:6<616::aid-ajmg8>3.0.co;2-i
• PubMed: 10581479
• Original source →

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Studies this one cites

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

• Association of apolipoprotein E allele ϵ4 with late‐onset familial and sporadic Alzheimer's disease Neurology · 1993-08-01 · usefulness score 65/100 · Genetics
• Alzheimer's disease in Down's syndrome: clinicopathologic studies Neurology · 1985-07-01 · usefulness score 61/100 · Getting a diagnosis
• Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease Proceedings of the National Academy of Sciences of the United States of America · 1993-03-01 · usefulness score 58/100 · Genetics
• The natural history of dementia in Down's syndrome Archives of neurology · 1990-03-01 · usefulness score 57/100 · Digital health tools
• Amyloid-associated proteins alpha 1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer beta-protein into filaments Nature · 1994-11-01 · usefulness score 57/100 · Genetics
• Genetic association between intronic polymorphism in presenilin-1 gene and late-onset Alzheimer's disease. Alzheimer's Disease Collaborative Group Lancet (London, England) · 1996-02-01 · usefulness score 54/100 · Genetics
• A prospective study of Alzheimer disease in Down syndrome Archives of neurology · 1989-08-01 · usefulness score 49/100 · How common it is

Later studies that cite this one

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• The 129 codon polymorphism of the prion protein gene influences earlier cognitive performance in Down syndrome subjects Journal of neurology · 2003-06-01 · usefulness score 37/100 · Down syndrome and Alzheimer's

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