Protein cause of memory lapse in old age

Researchers identify protein that causes age-related memory loss

08/30/2013

US scientists at Columbia University in New York have discovered how natural memory loss is caused in old age. A significant role plays thereby a lack „RbAp48, a histone-binding protein that modifies histone acetylation“, The research team reports to the Nobel Prize winner Eric Kandel in the specialist magazine „Science Translational Medicine“.

After investigating the brain of eight deceased patients, the researchers found a marked age-related decrease in the RbAp48 protein around the hippocampus, and in experiments with mice they examined whether this might be the trigger of memory decline in old age. It was not about the morbid impairments of memory, as seen in Alzheimer's disease, but about the naturally diminishing memory in old age. While Alzheimer's is associated with the deposition of so-called plaques in the brain, according to the researchers, the usual age-related memory loss is based on an undersupply in the area of ​​the hippocampus with the protein RbAp48.

Lack of RbAp48 Cause of memory lapse
According to the researchers, the investigation of human brains suggested that there may be an association between the memory weakness in old age and the age-related decline of RbAp48 in the hippocampus or its subsection of the dentate gyrus. „To test whether the RbAp48 decline could be responsible for age-related memory loss, we used mice and found that, in concert with humans, RbAp48 was less abundant in the dentate gyrus in old mice than in young mice“, the researchers write in the journal „ Science Translational Medicine“. In the next investigation step, genetically modified mice were produced in whose brain the RbAp48 proteins were inhibited. „Inhibition of RbAp48 in young mice causes hippocampus-dependent memory deficits similar to those associated with aging“, report Kandel and colleagues.

Age-related memory loss recoverable?
Unlike Alzheimer's, the age-related memory loss due to a RbAp48 deficiency but by appropriate delivery of RbAp48 or improved absorption can basically be repaired, the researchers explain. The experiments on the mice would have confirmed this. Thus, the memory of the aged mice had become significantly better after the RbAp48 release was artificially raised. This has the „age-related hippocampal-based memory loss and changes in histone acetylation“ relieved, write Kandel and colleagues. „Taken together, these results indicate that the dentate gyrus as a hippocampal region undergoes age-related changes and we have identified molecular mechanisms of cognitive aging that could be valid targets for therapeutic intervention“, so the conclusion of the US scientists.

Age forgetfulness is subject to other laws than Alzheimer's
The current investigation provides strong evidence that age-forgetfulness is subject to different laws than Alzheimer's, explained Kandel. Particularly encouraging is the success in addressing the memory loss of older mice by increasing the RbAp48 release. Here the researchers see considerable therapeutic potential for the future. Although it remains unclear whether other factors affect the age-related memory loss but it can be assumed that the lack of RbAp48 plays a crucial role, explained Eric Kandel. (Fp)