Fluorescent light-induced chromatid breaks distinguish Alzheimer disease cells from normal cells in tissue culture

Topic: Amyloid, tau and blood-test diagnosis

The neurodegeneration and amyloid deposition of sporadic Alzheimer disease (AD) also occur in familial AD and in all trisomy-21 Down syndrome (DS) patients, suggesting a common pathogenetic mechanism. We investigated whether defective processing of damaged DNA might be that mechanism, as postulated for the neurodegeneration in xeroderma pigmentosum, a disease with defective repair not only of UV radiation-induced, but also of some oxygen free radical-induced, DNA lesions. We irradiated AD and DS skin fibroblasts or blood lymphocytes with fluorescent light, which is known to cause free radical-induced DNA damage. The cells were then treated with either beta-cytosine arabinoside (araC) or caffeine, and chromatid breaks were quantified. At least 28 of 31 normal donors and 10 of 11 donors with nonamyloid neurodegenerations gave normal test results. All 12 DS, 11 sporadic AD, and 16 familial AD patients tested had abnormal araC and caffeine tests, as did XP-A cells. In one of our four AD families, an abnormal caffeine test was found in all 10 afflicted individuals (including 3 asymptomatic when their skin biopsies were obtained) and in 8 of 11 offspring at a 50% risk for AD. Our tests could prove useful in predicting inheritance of familial AD and in supporting, or rendering unlikely, the diagnosis of sporadic AD in patients suspected of having the disease.

Key findings

• At least 28 of 31 normal donors and 10 of 11 donors with nonamyloid neurodegenerations gave normal test results.

Why it matters

This cell study found abnormal chromatid break tests after fluorescent light irradiation in cells from all tested Down syndrome, sporadic Alzheimer and familial Alzheimer patients, unlike most normal donors. The authors suggest the test might help predict inherited familial Alzheimer disease, but it is a laboratory assay and not a treatment, cure or prevention.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1073/pnas.93.10.5146
• PubMed: 8643543
• Original source →
• Free full text: PubMed Central →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

@article{parshad1996-8643543,
  author  = {Parshad, R. P. and Sanford, K. K. and Price, F. M. and Melnick, L. K. and Nee, L. E. and Schapiro, M. B. and Tarone, R. E. and Robbins, J. H.},
  title   = {{Fluorescent light-induced chromatid breaks distinguish Alzheimer disease cells from normal cells in tissue culture}},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  year    = {1996},
  doi     = {10.1073/pnas.93.10.5146},
  pmid    = {8643543},
  url     = {https://doi.org/10.1073/pnas.93.10.5146}
}

Studies this one cites

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

• Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease Nature · 1995-06-01 · usefulness score 64/100 · Genetics
• 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
• X-ray-induced chromatid damage in cells from Down syndrome and Alzheimer disease patients in relation to DNA repair and cancer proneness Cancer genetics and cytogenetics · 1993-10-01 · usefulness score 36/100 · Down syndrome and Alzheimer's
• Hypersensitivity to ionizing radiation in cultured cells from Down syndrome patients Journal of the neurological sciences · 1985-05-01 · usefulness score 35/100 · Down syndrome and Alzheimer's

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1 study in the alzhub library lists this one in its references.

• Evidence against increased oxidative DNA-damage in Down syndrome Neuroscience letters · 1997-10-01 · usefulness score 40/100 · Down syndrome and Alzheimer's

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