Anna Maria Birkl-Toeglhofer, Austria
Medical University of Innsbruck Institute of Pathology, Neuropathology and Molecular PathologyPresenter of 2 Presentations
LIVE DISCUSSION
ALTERED PROTEIN TRANSLATION INITIATION MIGHT CONTRIBUTE TO ALZHEIMER’S DISEASE
Abstract
Aims
In Alzheimer’s disease (AD), pathological protein accumulation is a major hallmark represented by neurofibrillary tangles and amyloid plaques. This protein accumulation might be due to a dysregulated protein synthesis. The regulation of eukaryotic protein synthesis is primarily effected by eukaryotic initiation factors (eIFs) at the translation initiation step. So far, the role of eIFs in neurodegeneration and their potential contribution to neurodegenerative processes are not fully understood. Here, we aimed to reveal the expression patterns of eIF subunits in AD.
Methods
eIFs were analyzed on mRNA and protein level in human post mortem brain tissue including regions of frontal and temporal cortices and the hippocampus. AD subjects and controls without neurodegenerative pathology were investigated. For the neuropathological assessment, Braak and Braak staging was performed for all samples.
Results
The expression of eIF4G on mRNA and protein level was decreased in higher Braak and Braak stages. Increased eIF4G levels were present in hippocampal tissue of AD subjects. Beside eIF4G, altered expression was observed for other eIF subunits such as eIF3 subunits.
Conclusions
In human post mortem brain tissue, several eIF subunits were found to be altered in AD, whereas alterations are already present on gene expression level. It might be that translation initiation is reduced in AD subjects with advanced AD pathology represented by the Braak and Braak staging. Overall, a potential involvement of an affected translation initiation and a contribution of individual eIF subunits to AD pathology can be assumed.