Decreased base excision repair and increased helicase activity in Alzheimer's disease brain

Mark A. Lovell, Chengsong Xie, William R. Markesbery

Research output: Contribution to journalArticlepeer-review

147 Scopus citations

Abstract

Recent studies show an increase in DNA oxidation in brain and cerebrospinal fluid (CSF), and decreased levels of the free repair product in CSF in Alzheimer's disease (AD). This is a study of the activity of the base excision repair enzyme, 8-oxoguanine glycosylase (responsible for the excision of 8-oxoguanine), and DNA helicase activity in nuclear protein samples from four brain regions of 10 AD and eight age-matched control subjects. Statistically significant (p < 0.05) decreases in 8-oxoguanine glycosylase activity were observed in the nuclear fraction of AD hippocampal and parahippocampal gyri (HPG), superior and middle temporal gyri (SMTG), and inferior parietal lobule (IPL). DNA helicase activity was elevated in all nuclear samples except the IPL with statistically significant elevations in the HPG and CER. Statistically significant depletion of helicase activity was observed in the nuclear fraction in AD IPL. Our results demonstrate that the repair capabilities for 8-oxoguanine are decreased in AD. The modest increase in DNA helicase activity in some brain regions in AD may interfere with base excision repair mechanisms. Overall, the decreased repair of DNA damage could be involved in the pathogenesis of neurodegeneration in AD. (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)116-123
Number of pages8
JournalBrain Research
Volume855
Issue number1
DOIs
StatePublished - Feb 7 2000

Bibliographical note

Funding Information:
This work was supported by NIH grants 5P50-AGO5144 and 1PO1-AGO5119, and a grant from the Abercrombie Foundation. The authors thank Drs. Daron Davis and David Wekstein for tissue procurement, Ms. Jane Meara and Mr. Cecil Runyons for technical assistance, and Ms. Paula Thomason for editorial assistance.

Keywords

  • Alzheimer's disease
  • Base excision repair
  • DNA oxidation
  • DNA repair
  • Helicases

ASJC Scopus subject areas

  • Neuroscience (all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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