Mechanisms of Memory Impairment in Alzheimer's Disease
This is an example of ongoing work on one narrow slice of the exceptionally complex mechanisms of Alzheimer's disease. It is worth considering that while Alzheimer's is the high level call to action, the real work is the business of understanding the fine details of the brain. This is the often the way in medical research: treating cancer was the call to action that funded research leading to our present understanding of cellular biochemistry in regeneration, replication, and development. The hue and cry of AIDS activism was the call to action that funded the development of our present understanding of viruses, much increased these past three decades. So it is for Alzheimer's and the biochemistry of the mind.
A new study has identified activity of brain proteins associated with memory impairments in Alzheimer's disease, and has also found that "repairing" this activity leads to an improvement in memory. "In the study we found that the nerve cells in the mouse models of Alzheimer face a type of metabolic stress. When a cell faces such metabolic stress, it is logical that it will reduce its activity level in order to survive. The problem is that this stress is chronic and leads to impairment of cognitive functioning."In a previous study, researchers found a connection between abnormal activity of the elF2 protein, which is known to regulate the formation of new proteins needed for the creation of long-term memories, and mice that carried the human gene APOE4, which is known as a key risk factor for sporadic Alzheimer's. In the present study, a group of young mice carrying the human gene APOE4 showed cognitive impairment on the behavioral level - in other words, they showed signs of damage on the level of spatial memory. A molecular examination showed that the protein elF2 had undergone phosphorylation, changing its action and leading to several processes, including elevated expression of the RNA on another protein, ATF4. This elevation delayed the expression of additional genes associated with the consolidation of memory - i.e. the creation of long-term stable memory.
"The abnormal activity in the regulation of the activity of the ATF4 probably causes the cell to 'feel' that is under stress, that is - overactive. A cell that is in stress reduces its activity in order to survive with the goal of restoring it to a normal condition after the stress passes. The problem is that in Alzheimer's the stress is probably chronic, and accordingly there is no return to normal activity." In order to reinforce the connection they found, the researchers performed an additional intervention in which they prevented eIF2 from causing an increase in the RNA of the ATF4. When they examined these mice, they found an improvement in their cognitive capabilities.