- Arrangement: (København)
- Arrangør: Alfred Benzon Foundation
Alzheimer’s disease (AD) is a progressive, multifactorial neurodegenerative disorder that is the main cause of dementia globally. AD is clinically well characterized, however, little is known about the early etiology. Aging is the greatest risk factor for the development of dementia including AD, and age-related changes are augmented in patients with AD. Increased oxidative stress, resulting from imbalance in production and clearance of reactive oxygen species (ROS), can damage DNA and other macromolecules, leading to genome instability and disrupted cellular functions.
Oxidative DNA damage is primarily repaired by the base excision repair (BER) pathway, however, the nucleotide excision repair (NER) pathway repairing helix distorting damages also seems to be involved. NER is known to be associated with neurodegenerative disorders like Cockayne syndrome and some subtypes of Xeroderma pigmentosum, and may play a role in the early stages of AD. To this end, we addressed the role of the NER pathway in the development of AD by comparing the expression of the DNA repair components RAD23B, RPA1, ERCC1, LIG3, PCNA and MPG in blood and post-mortem brain tissue from patients with AD, mild cognitive impairment (MCI) and healthy controls (HC). mRNA levels of the DNA repair components selected were significantly higher in the brain compared to blood. Notably, the expression of LIG3 (frontal cortex) and RPA1 (cerebellum) was higher in the AD brain than in healthy controls. This suggests an important role of NER in the brain relevant for the etiology of AD.