Increased low-level chromosome 21 mosaicism in older individuals with Down syndrome

Topic: Brain proteins, microglia and lab models

During a study of the familial aggregation of Down syndrome (DS) and Alzheimer disease (AD), we observed an increase in mosaicism for disomy 21 in older individuals with DS. In a total of 213 DS subjects who were studied cytogenetically, only 1 of 121 (0.8%) under age 45 exhibited mosaicism, while 14 of 92 (15.2%) who were age 45 or older had mosaicism. Mosaicism in this report connotes "low-level" mosaicism, where all 15 individuals exhibited a modal chromosome number of 47 (i.e., trisomy 21), and at least two cells lacked one of the three chromosomes 21. The occurrence of aneuploidy for chromosomes 15, 17, and X increased with age, and an inverse correlation between chromosome loss and size was also observed. Because older individuals had not been karyotyped at birth, it was not possible to determine whether our observations were due to either increased survival of mosaic individuals or accumulation of disomy 21 cells via increased chromosome loss with aging of the trisomy 21 individual. Using a modeling approach involving life table methods, we obtained results that suggested acquired mosaicism as the predominant mechanism to explain our findings. These results support the hypothesis that as individuals with DS age, there is an increased loss of chromosome 21.

@article{jenkins1997-9028448,
  author  = {Jenkins, E. C. and Schupf, N. and Genovese, M. and Ye, L. L. and Kapell, D. and Canto, B. and Harris, M. and Devenny, D. and others},
  title   = {{Increased low-level chromosome 21 mosaicism in older individuals with Down syndrome}},
  journal = {American journal of medical genetics},
  year    = {1997},
  doi     = {10.1002/(sici)1096-8628(19970120)68:2<147::aid-ajmg5>3.0.co;2-m},
  pmid    = {9028448},
  url     = {https://doi.org/10.1002/(sici)1096-8628(19970120)68:2<147::aid-ajmg5>3.0.co;2-m}
}

Key findings

• During a study of the familial aggregation of Down syndrome (DS) and Alzheimer disease (AD), we observed an increase in mosaicism for disomy 21 in older individuals with DS.
• Using a modeling approach involving life table methods, we obtained results that suggested acquired mosaicism as the predominant mechanism to explain our findings.
• These results support the hypothesis that as individuals with DS age, there is an increased loss of chromosome 21.

Why it matters

This cytogenetic study found that older people with Down syndrome were more likely to have some cells that had lost a copy of chromosome 21, suggesting chromosome loss increases with age. The finding is about cell biology and does not directly address treating, curing, or preventing Alzheimer's disease.

Study details

• Participants15
• Effect size0.8%; 15.2%
• Evidence strengthLow

Read the original

• DOI: 10.1002/(sici)1096-8628(19970120)68:2<147::aid-ajmg5>3.0.co;2-m
• PubMed: 9028448
• 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.

• A prospective study of Alzheimer disease in Down syndrome Archives of neurology · 1989-08-01 · usefulness score 49/100 · How common it is
• Age-associated chromosome 21 loss in Down syndrome: possible relevance to mosaicism and Alzheimer disease American journal of medical genetics · 1993-03-01 · usefulness score 34/100 · Down syndrome and Alzheimer's

Later studies that cite this one

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

• The effects of mosaicism on biological and clinical markers of Alzheimer's disease in adults with Down syndrome EBioMedicine · 2024-11-04 · usefulness score 56/100 · Down syndrome and Alzheimer's
• Alzheimer disease and Down syndrome: factors in pathogenesis Neurobiology of aging · 2005-03-01 · usefulness score 43/100 · Down syndrome and Alzheimer's

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• The value of the Rivermead Behavioural Memory Test (Children's Version) in an epidemiological study of older adults with Down syndrome The British journal of clinical psychology · 1998-02-01 · usefulness score 46/100

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• Detection of Alzheimer disease in individuals with Down syndrome American journal of mental retardation : AJMR · 1995-05-01 · usefulness score 34/100 · Down syndrome and Alzheimer's
• Croatian population data for arylsulfatase a pseudodeficiency-associated mutations in healthy subjects, and in patients with Alzheimer-type dementia and Down syndrome Archives of medical research · 2002-09-01 · usefulness score 34/100 · Down syndrome and Alzheimer's
• “Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene-dose-sensitive AD-suppressor in human brain” Molecular psychiatry · 2020-01-31 · usefulness score 42/100 · Down syndrome and Alzheimer's

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• Construction of human chromosome 21-specific yeast artificial chromosomes 1989 · Down syndrome and Alzheimer's
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More on Down syndrome and Alzheimer's

• A review that covers this ground Mosaicism for trisomy 21 in a patient with young-onset dementia: a case report and brief literature review Archives of neurology · 2008-03-01 · usefulness score 42/100
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