A neuronal DNA damage response is detected at the earliest stages of Alzheimer's neuropathology and correlates with cognitive impairment in the Medical Research Council's Cognitive Function and Ageing Study ageing brain cohort.

ABSTRACT:

Aims

Population-based studies have shown that approximately 20% of the ageing population (aged 65 years and over) with dementia have little or no classical Alzheimer-type neuropathology. Cumulative DNA damage and a reduced capacity of DNA repair may result in neuronal dysfunction and contribute to cognitive impairment independent of Alzheimer-type pathology in the ageing brain.

Methods

We investigated expression of the DNA damage response (DDR)-associated molecules γH2AX and DNA-PKcs using immunohistochemistry and western blotting, and senescence-associated β-galactosidase in the frontal association neocortex of cases with low levels of Alzheimer-type pathology (Braak & Braak stage 0-II), and explored their relationship to cognitive impairment in a population-representative

SUBMITTER: Simpson JE 

PROVIDER: S-EPMC4861215 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature