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Defective Dna Base Excision Repair In Brain From Individuals With Alzheimer's Disease And Amnestic Mild Cognitive Impairment, Lior Weissman, Dong-Gyu Jo, Martin M. Sørensen, Nadja C. De Souza-Pinto, William R. Markesbery, Mark P. Mattson, Vilhelm A. Bohr Aug 2007

Defective Dna Base Excision Repair In Brain From Individuals With Alzheimer's Disease And Amnestic Mild Cognitive Impairment, Lior Weissman, Dong-Gyu Jo, Martin M. Sørensen, Nadja C. De Souza-Pinto, William R. Markesbery, Mark P. Mattson, Vilhelm A. Bohr

Pathology and Laboratory Medicine Faculty Publications

Oxidative stress is thought to play a role in the pathogenesis of Alzheimer's disease (AD) and increased oxidative DNA damage has been observed in brain tissue from AD patients. Base excision repair (BER) is the primary DNA repair pathway for small base modifications such as alkylation, deamination and oxidation. In this study, we have investigated alterations in the BER capacity in brains of AD patients. We employed a set of functional assays to measure BER activities in brain tissue from short post-mortem interval autopsies of 10 sporadic AD patients and 10 age-matched controls. BER activities were also measured in brain …


Oxidative Dna Damage In Mild Cognitive Impairment And Late-Stage Alzheimer's Disease, Mark A. Lovell, William R. Markesbery Jan 2007

Oxidative Dna Damage In Mild Cognitive Impairment And Late-Stage Alzheimer's Disease, Mark A. Lovell, William R. Markesbery

Chemistry Faculty Publications

Increasing evidence supports a role for oxidative DNA damage in aging and several neurodegenerative diseases including Alzheimer's disease (AD). Attack of DNA by reactive oxygen species (ROS), particularly hydroxyl radicals, can lead to strand breaks, DNA–DNA and DNA–protein cross-linking, and formation of at least 20 modified bases adducts. In addition, α,β-unsaturated aldehydic by-products of lipid peroxidation including 4-hydroxynonenal and acrolein can interact with DNA bases leading to the formation of bulky exocyclic adducts. Modification of DNA bases by direct interaction with ROS or aldehydes can lead to mutations and altered protein synthesis. Several studies of DNA base adducts in late-stage …