A prominent level of neuronal oxidative damage distinguishes MCI from preclinical stage of Alzheimer’s disease

A prominent level of neuronal oxidative damage distinguishes MCI from preclinical stage of Alzheimer's disease

Akihiko Nunomura, Toshio Tamaoki

Department of Neuropsychiatry, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi

Although neuronal oxidative damage is an established feature in Alzheimer disease (AD), neuronal oxidative damage in the transitional stages from normal elderly to the onset of AD has not been fully examined. Using an in situ approach to identify 8-hydroxyguanosine (8-OHG), a steady-state marker of oxidative damage, we investigated levels of neuronal oxidative damage in brain samples from elderly who were rigorously evaluated for their pre-mortem score on the clinical dementia rating and post-mortem brain pathology. Relative density measurements of 8-OHG immunoreactions revealed that the neurons of the temporal cortex in subjects with mild cognitive impairment, but not preclinical AD, showed higher burden of oxidative damage compared to age-matched controls. A prominent level of neuronal oxidative damage is associated with the earliest changes marking the onset of cognitive impairment in the prodromal stage of AD.

Address correspondence to Dr. Akihiko Nunomura, Department of Neuropsychiatry, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi (Chuo, Yamanashi 409-3898, Japan)