University study may lead to Alzheimer’s treatments
University of Haifa researchers discover a link between dementia and the activity level of a protein called eIF2alpha.
By JUDY SIEGEL-ITZKOVICHBrain with Alheimer's 521(photo credit: Wikimedia commons)
A new clue to Alzheimer’s disease has been found by University of Haifa researchers.They discovered a link between dementia, which is reaching epidemic proportions due to aging of the world’s population, and the activity level of a protein called eIF2alpha. The study, recently published in the journal Neurobiology of Aging, brings hope for eventual new treatments.Prof. Kobi Rosenblum, head of the university’s Sagol Department of Neurobiology, said that altering the performance of this protein through drug therapy could constitute a treatment for the incurable, progressive disease.Alzheimer’s research has mainly focused in recent years on battling the disease once symptoms have appeared, even though researchers have known for years that it is present in the brain for many years before symptoms make their presence known.In advanced stages of the disease, Rosenblum explained, small lumps of amyloid protein called plaques are identified forming in the brain. These plaques, he said, are typical of Alzheimer’s sufferers and undermine brain functioning.Much research has been directed at understanding these plaques and trying to eliminate them or to restrict their formation and growth.Research has also involved mostly familial (genetically transmitted) dementia, which is caused by known mutations. This new research tried to understand the mechanisms in the development of Alzheimer’s that are linked to molecular response to the metabolic distress that increases with age.The study, conducted by research student Yifat Segev in the Haifa university’s Laboratory for Research of Molecular and Cellular Mechanisms Underlying Learning and Memory that is headed by Rosenblum, in cooperation with Prof. Danny Michaelson of Tel Aviv University, sought to identify factors that could be linked to Alzheimer’s even before the plaques are formed and that are connected to age, the disease’s primary risk factor.According to Segev, this is the first time that a link has been found between the activity of eIF2alpha and the Apoe4 gene in relation to Alzheimer’s disease. She noted that modification treatments for the eIF2alpha mechanism are being widely researched and are developing quickly, and that the more that can be understood about the connection between this mechanism and Alzheimer’s, the more researchers can find ways to identify and slow the progress of the disease.A previous study coauthored by Canadian researchers and Rosenblum’s lab revealed that cognitive abilities could be improved by altering the activity of the eIF2alpha protein, which regulates the creation of proteins in all cells, including nerve cells. That research gave Alzheimer’s researchers a glimmer of hope: Perhaps it would be possible to improve cognitive abilities or even prevent cognitive damage in Alzheimer’s patients at an early stage of the disease by intervening in the mechanisms that regulate protein generation in nerve cells.
The current study compared mice that expressed the human Apoe4 gene – known as a central risk factor for Alzheimer’s – with a group of mice with the parallel Apoe3 gene, which does not constitute a risk factor for the disease.Mice in the former group showed a change in the regulating mechanism for protein generation involving the eIF2alpha protein that damaged the cognitive abilities of those mice at a young age. This sort of mechanism change is characteristic of aging, and so also hints at the tendency of these mice toward premature aging.
