Abstract
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 samples from 9 amnestic mild cognitive impairment (MCI) subjects. We found significant BER deficiencies in brains of AD patients due to limited DNA base damage processing by DNA glycosylases and reduced DNA synthesis capacity by DNA polymerase β. The BER impairment was not restricted to damaged brain regions and was also detected in the brains of amnestic MCI patients, where it correlated with the abundance of neurofibrillary tangles. These findings suggest that BER dysfunction is a general feature of AD brains which could occur at the earliest stages of the disease. The results support the hypothesis that defective BER may play an important role in the progression of AD.
Document Type
Article
Publication Date
8-2007
Digital Object Identifier (DOI)
http://dx.doi.org/10.1093/nar/gkm605
Repository Citation
Weissman, Lior; Jo, Dong-Gyu; Sørensen, Martin M.; de Souza-Pinto, Nadja C.; Markesbery, William R.; Mattson, Mark P.; and Bohr, Vilhelm A., "Defective DNA Base Excision Repair in Brain from Individuals with Alzheimer's Disease and Amnestic Mild Cognitive Impairment" (2007). Pathology and Laboratory Medicine Faculty Publications. 10.
https://uknowledge.uky.edu/pathology_facpub/10
Notes/Citation Information
Published in Nucleic Acids Research, v. 35, no. 16, p. 5545-5555.
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.