title: Altered DNA base excision repair profile in brain tissue and blood in Alzheimer's disease.
abstract: Alzheimer's disease (AD) is a progressive, multifactorial neurodegenerative disorder that is the main cause of dementia globally. AD is associated with increased oxidative stress, resulting from imbalance in production and clearance of reactive oxygen species (ROS). ROS can damage DNA and other macromolecules, leading to genome instability and disrupted cellular functions. Base excision repair (BER) plays a major role in repairing oxidative DNA lesions. Here, we compared the expression of BER components APE1, OGG1, PARP1 and Polβ in blood and postmortem brain tissue from patients with AD, mild cognitive impairment (MCI) and healthy controls (HC).
  
  
  
  BER mRNA levels were correlated to clinical signs and cerebrospinal fluid biomarkers for AD. Notably, the expression of BER genes was higher in brain tissue than in blood samples. Polβ mRNA and protein levels were significantly higher in the cerebellum than in the other brain regions, more so in AD patients than in HC. Blood mRNA levels of OGG1 was low and PARP1 high in MCI and AD.
  
  
  
  These findings reflect the oxidative stress-generating energy-consumption in the brain and the importance of BER in repairing these damage events. The data suggest that alteration in BER gene expression is an event preceding AD. The results link DNA repair in brain and blood to the etiology of AD at the molecular level and can potentially serve in establishing novel biomarkers, particularly in the AD prodromal phase.
authors.affiliation: Department of Microbiology, Oslo University Hospital, Oslo, Norway.|Department of Microbiology, University of Oslo, Oslo, Norway.
authors.forename: Meryl S
authors.initials: MS
authors.lastname: Lillenes
authors.affiliation: Fundación Centro Investigación Enfermedades Neurológicas (CIEN), Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Rabano
authors.affiliation: Department of Microbiology, Oslo University Hospital, Oslo, Norway.|Department of Microbiology, University of Oslo, Oslo, Norway.
authors.forename: Mari
authors.initials: M
authors.lastname: Støen
authors.affiliation: Department of Microbiology, Oslo University Hospital, Oslo, Norway.
authors.forename: Tahira
authors.initials: T
authors.lastname: Riaz
authors.affiliation: Department of Microbiology, Oslo University Hospital, Oslo, Norway.|Department of Microbiology, University of Oslo, Oslo, Norway.
authors.forename: Dorna
authors.initials: D
authors.lastname: Misaghian
authors.affiliation: Department of Microbiology, Oslo University Hospital, Oslo, Norway.
authors.forename: Linda
authors.initials: L
authors.lastname: Møllersen
authors.affiliation: Department of Clinical Molecular Biology and Laboratory Sciences (EpiGen), Division of Medicine, Akershus University Hospital and University of Oslo, Lørenskog, Norway.
authors.forename: Ying
authors.initials: Y
authors.lastname: Esbensen
authors.affiliation: Norwegian Computing Center, Oslo, Norway.
authors.forename: Clara-Cecilie
authors.initials: CC
authors.lastname: Günther
authors.affiliation: Department of Neurology, Faculty Division, Akershus University Hospital, University of Oslo, Lørenskog, Norway.
authors.forename: Per
authors.initials: P
authors.lastname: Selnes
authors.affiliation: Department of Neurology, Faculty Division, Akershus University Hospital, University of Oslo, Lørenskog, Norway.
authors.forename: Vidar T V
authors.initials: VT
authors.lastname: Stenset
authors.affiliation: Department of Neurology, Faculty Division, Akershus University Hospital, University of Oslo, Lørenskog, Norway.
authors.forename: Tormod
authors.initials: T
authors.lastname: Fladby
authors.affiliation: Department of Microbiology, Oslo University Hospital, Oslo, Norway. tone.tonjum@medisin.uio.no.|Department of Microbiology, University of Oslo, Oslo, Norway. tone.tonjum@medisin.uio.no.|Department of Microbiology, University of Oslo, Oslo University Hospital, Postbox 4950 Nydalen, Oslo, NO-0424, Norway. tone.tonjum@medisin.uio.no.
authors.forename: Tone
authors.initials: T
authors.lastname: Tønjum
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000235:genetics*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism; D019951:DNA Polymerase beta / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair / Q000235:genetics*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000235:genetics / Q000378:metabolism; D062706:Prodromal Symptoms; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D017423:Sequence Analysis, RNA
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D019951:DNA Polymerase beta; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase
keywords: APE1; Alzheimer’s disease; Base excision repair; Brain tissue; DNA glycosylase OGG1; DNA polymerase Polβ; DNA repair; PARP1