Deficient Repair of Alkylation Damage of DNA in Alzheimer’s Disease and Amyotrophic Lateral Sclerosis Cells

  • W. G. Bradley
  • S. H. Robison
  • R. Tandan
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 209)


The etiology of amyotrophic lateral sclerosis (ALS) is still unknown. There are many pieces of evidence linking ALS, Alzheimer’s disease and Parkinson’s disease. These include the occasional clinical association of the conditions in the same patient and the same family, the endemic foci of all three diseases, and the presence of changes of one disease in the central nervous system of some patients dying of another of these diseases. There are several indications that alterations in genetic material may exist in these diseases, including decrease in nuclear and nucleolar size[l], alteration in chromatin of neurons[2] and decrease in transcriptionally active chromatin[3]. A possible DNA repair defect was implicated when it was observed that lymphocytes, lymphoblasts and skin fibroblasts from several different neurodegenerative disorders, including Alzheimer’s disease and ALS were more sensitive to DNA alkylating agents[4,5]. It has also been reported that lymphocytes from Alzheimer’s disease patients have increased sensitivity to bleomycin, 4-nitroquinoline- 1-oxide and mitomycin C which produce various other forms of DNA damage[6]. We have further investigated the hypothesis that a DNA repair defect occurs in both of these diseases and offer direct evidence of a DNA repair defect in skin fibroblasts from ALS and Alzheimer’s disease patients after exposure to an alkylating agent.


Amyotrophic Lateral Sclerosis Skin Fibroblast Motor Neuron Disease Population Doubling Level Methyl Methane Sulfonate 
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Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • W. G. Bradley
    • 1
    • 2
  • S. H. Robison
    • 1
  • R. Tandan
    • 1
  1. 1.Department of NeurologyUniversity of Vermont College of MedicineBurlingtonUSA
  2. 2.Department of NeurologyBurlingtonUSA

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