Cell-Type-Specific Differences in Age-Related Changes of DNA Repair in the Mouse Brain - Molecular Basis for a New Approach to Understand the Selective Neuronal Vulnerability in Alzheimer's Disease.

Despite intensive research over the last decades, the molecular basis of the selective neuronal vulnerability in Alzheimer's disease (AD) is still largely unknown. In this context we have recently shown by means of quantitative autoradiography that presumably all types of neurons in the mouse brain suffer an age-related decrease in the rate of mitochondrial DNA synthesis, while in contrast only some distinct types of neurons showed a decrease in the rate of spontaneous overall nuclear DNA repair measured as unscheduled nuclear DNA synthesis. Most strikingly, there was a highly positive correlation to be found between that group of neurons in the mouse brain showing the age-related decrease in the rate of spontaneous overall nuclear DNA repair (pattern X) and the pattern of neurons in the human brain which - according to the literature - are affected by the formation of neurofibrillary tangles in AD (pattern Y).