Age-associated chromosome 21 loss in Down syndrome: possible relevance to mosaicism and Alzheimer disease

Topic: Amyloid, tau and blood-test diagnosis

We previously observed low level mosaicism (2-4% normal cells) in phytohemagglutinin-stimulated peripheral blood lymphocytes (PBL) in 29% of a small group of elderly persons with Down syndrome (DS). An analysis of cytogenetic data on 154 trisomy 21 cases (age 1 day to 68 years) showed that the proportion of diploid cells in such cultures significantly increased (P < 0.005) with advancing age. Thus, the "occult" mosaicism in PBL of the elderly persons with DS is likely due to the accumulation of cells that have lost a chromosome 21. A consequence of chromosome 21 loss could be uniparental disomy of the 2n cells, a factor that might have significant biological consequences if some chromosome 21 genes are imprinted. Loss of a chromosome 21 from trisomic cells might result in tissue-specific mosaicism and "classical" mosaicism in different age groups. Chromosome 21 loss might also be relevant to the development of Alzheimer-type dementia in DS and in the general population.

@article{percy1993-8456829,
  author  = {Percy, M. E. and Markovic, V. D. and Dalton, A. J. and McLachlan, D. R. and Berg, J. M. and Rusk, A. C. and Somerville, M. J. and Chodakowski, B. and others},
  title   = {{Age-associated chromosome 21 loss in Down syndrome: possible relevance to mosaicism and Alzheimer disease}},
  journal = {American journal of medical genetics},
  year    = {1993},
  doi     = {10.1002/ajmg.1320450513},
  pmid    = {8456829},
  url     = {https://doi.org/10.1002/ajmg.1320450513}
}

Key findings

• An analysis of cytogenetic data on 154 trisomy 21 cases (age 1 day to 68 years) showed that the proportion of diploid cells in such cultures significantly increased (P < 0.005) with advancing age.
• A consequence of chromosome 21 loss could be uniparental disomy of the 2n cells, a factor that might have significant biological consequences if some chromosome 21 genes are imprinted.
• Loss of a chromosome 21 from trisomic cells might result in tissue-specific mosaicism and "classical" mosaicism in different age groups.

Why it matters

This analysis of cytogenetic data found that the proportion of diploid cells increased with age in people with trisomy 21, suggesting loss of a chromosome 21 over time. The authors propose this might be relevant to Alzheimer-type dementia, but this is a hypothesis and no treatment or prevention is tested.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1002/ajmg.1320450513
• PubMed: 8456829
• 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.

• Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease Nature · 1991-02-21 · usefulness score 63/100 · Genetics
• Alzheimer's disease in Down's syndrome: clinicopathologic studies Neurology · 1985-07-01 · usefulness score 61/100 · Getting a diagnosis
• Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease Neurology · 1984-07-01 · usefulness score 58/100 · Getting a diagnosis
• Red cell superoxide dismutase, glutathione peroxidase and catalase in Down syndrome patients with and without manifestations of Alzheimer disease American journal of medical genetics · 1990-04-01 · usefulness score 38/100 · 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
• Increased low-level chromosome 21 mosaicism in older individuals with Down syndrome American journal of medical genetics · 1997-01-01 · usefulness score 39/100 · Down syndrome and Alzheimer's

Related studies in Down syndrome and Alzheimer's

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• The evolution of ovarian oocyte decline with aging and possible relationships to Down syndrome and Alzheimer disease Experimental gerontology · 1994-05-01 · usefulness score 35/100
• Molecular abnormalities of the brain in Down syndrome: relevance to Alzheimer's neurodegeneration Journal of neural transmission. Supplementum · 1999-01-01 · usefulness score 43/100
• Alzheimer dementia in Down's syndrome: the relevance of cognitive ability Journal of intellectual disability research : JIDR · 2001-02-01 · usefulness score 35/100
• Neurofibrillary tangles, granulovacuolar degeneration, and neuron loss in Down Syndrome: quantitative comparison with Alzheimer dementia Annals of neurology · 1980-05-01 · usefulness score 43/100

Also tagged “down”

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• Quantification of modified amyloid beta peptides in Alzheimer disease and Down syndrome brains Journal of neuropathology and experimental neurology · 1998-11-01 · usefulness score 40/100 · Down syndrome and Alzheimer's
• Assessment of cognitive decline associated with aging: a comparison of individuals with Down syndrome and other etiologies Research in developmental disabilities · 1995-01-01 · usefulness score 32/100 · Down syndrome and Alzheimer's
• Extracellular deposits of A beta produced in cultures of Alzheimer disease brain vascular smooth muscle cells Journal of neuropathology and experimental neurology · 2005-01-01 · usefulness score 35/100 · Down syndrome and Alzheimer's

Similar studies

• Comparative mapping of DNA markers from the familial Alzheimer disease and Down syndrome regions of human chromosome 21 to mouse chromosomes 16 and 17 1988 · Down syndrome and Alzheimer's
• Mosaicism for trisomy 21 in a patient with young-onset dementia: a case report and brief literature review 2008 · Down syndrome and Alzheimer's
• Mapping of the gene encoding the beta-amyloid precursor protein and its relationship to the Down syndrome region of chromosome 21 1988 · Down syndrome and Alzheimer's
• The pathological association between Down syndrome and Alzheimer disease 1988 · Down syndrome and Alzheimer's
• The Genetics and Mechanisms of Alzheimer's Disease in Down Syndrome 2026 · Down syndrome and Alzheimer's
• Alzheimer's disease associated with Down syndrome: a genetic form of dementia 2021 · Prevention and risk

More on Down syndrome and Alzheimer's

• A review that covers this ground Loss of Proteostasis and Early-Onset Neurodegeneration in Down Syndrome: From Mechanisms to Interventions Antioxidants (Basel, Switzerland) · 2026-04-21 · usefulness score 39/100
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