Differential expression of phosphorylated translation initiation factor 2 alpha in Alzheimer's disease and Creutzfeldt–Jakob's disease.

Studies in vitro have shown that phosphorylated translation initiation factor 2α (TIF 2α) may have several functions, including regulation of protein synthesis, control of cell death and procurement of resistance to oxidative stress in nerve cells. These properties may have implications in certain human neurodegenerative diseases, such as Alzheimer's disease (AD) and Creutzfeldt–Jakob's disease (CJD), in which oxidative stress appears to be involved in the process of neurodegeneration and neurone death. Single and double-labelling immunohistochemistry to phosphorylated TIF 2α, phosphorylated SAPK/JNK, phosphorylated p38, tau , Cu/Zn superoxide dismutase 1 (SOD 1) and cleaved caspase-3 (17 kDa), and in situ end-labelling of nuclear DNA fragmentation, was carried out in postmortem samples of 10 patients with AD (stages III and VI of Braak and Braak), seven patients with CJD (five cases with methionine/methionine and two cases with methionine/valine at the codon 129 of the PrP gene) and eight age-matched controls. No phosphorylated TIF 2α immunoreactivity was found in control brains, but strong phosphorylated TIF 2α expression was observed in subpopulations of neurones bearing neurofibrillary tangles (NFTs) or pretangles in the hippocampus, entorhinal cortex and isocortex in AD. Phosphorylated TIF 2α is restricted to neurones with abnormal tau deposition, but only approximately 80% of neurones with NFTs in the hippocampus and 60% in the isocortex colocalize phosphorylated TIF 2α, thus indicating that not all neurones with NFTs over-express phosphorylated TIF 2α. Moreover, phosphorylated TIF 2α immunoreactivity was found in a percentage of neurones expressing phosphorylated SAPK/JNK and p38, which, in turn, are involved in tau phosphorylation in AD. However, dystrophic neurites of senile plaques that contain abnormal tau and express SOD 1 are negative to antiphosphorylated TIF 2α antibodies. Smooth... [ABSTRACT FROM AUTHOR]