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Neurosci Lett. 2018 Apr 13;672:53-58. doi: 10.1016/j.neulet.2018.02.043. Epub 2018 Feb 21.

Expression of nucleotide excision repair in Alzheimer's disease is higher in brain tissue than in blood.

Author information

1
Department of Microbiology, University of Oslo, Oslo, Norway. Electronic address: h.l.b.jensen@studmed.uio.no.
2
Department of Microbiology, University of Oslo, Oslo, Norway; Department of Microbiology, Oslo University Hospital, Oslo, Norway. Electronic address: m.s.lillenes@medisin.uio.no.
3
Centro Investigación Enfermedades Neurológicas (CIEN), Spain. Electronic address: arabano@fundacioncien.es.
4
Norwegian Computing Center, Oslo, Norway. Electronic address: clara-cecilie.gunther@nr.no.
5
Department of Microbiology, Oslo University Hospital, Oslo, Norway. Electronic address: Tahira.riaz@medisin.uio.no.
6
Department of Microbiology, Oslo University Hospital, Oslo, Norway. Electronic address: s.k.teklehaimanot@medisin.uio.no.
7
The Memory Clinic, Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway. Electronic address: inguls@ous-hf.no.
8
Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway. Electronic address: thomas.bohmer@medisin.uio.no.
9
Department of Microbiology, University of Oslo, Oslo, Norway; Department of Microbiology, Oslo University Hospital, Oslo, Norway. Electronic address: tone.tonjum@medisin.uio.no.

Abstract

Age-related changes are increased in patients with Alzheimer's disease (AD), including oxidative stress and DNA damage. We propose that genotoxic stress and DNA repair responses influence neurodegeneration in the pathogenesis of AD. Here, we focus on nucleotide excision repair (NER). Real-time qPCR and mass spectrometry were employed to determine the expression levels of selected NER components. The mRNA levels of the genes encoding the NER proteins RAD23B, RPA1, ERCC1, PCNA and LIG3 as well as the NER-interacting base excision repair protein MPG in blood and brain tissue from four brain regions in patients with AD or mild cognitive impairment and healthy controls (HC), were assessed. NER mRNA levels were significantly higher in brain tissue than in blood. Further, LIG3 mRNA levels in the frontal cortex was higher in AD versus HC, while mRNA levels of MPG and LIG3 in entorhinal cortex and RPA1 in the cerebellum were lower in AD versus HC. In blood, RPA1 and ERCC1 mRNA levels were lower in AD patients than in HC. Alterations in gene expression of NER components between brain regions were associated with AD, connecting DNA repair to AD pathogenesis and suggesting a distinct role for NER in the brain.

KEYWORDS:

Alzheimer’s disease; Brain; DNA repair; Neurodegenerative diseases

PMID:
29474873
DOI:
10.1016/j.neulet.2018.02.043
[Indexed for MEDLINE]
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