Protein behind age-related memory loss found

Scientists have discovered that a brain protein deficiency significantly contributes to age-related memory loss.
A team of researchers, led by Nobel laureate Eric R Kandel, has found that deficiency of RbAp48 in the hippocampus is a significant contributor to age-related memory loss and that this form of memory loss is reversible.
The study conducted in postmortem human brain cells and in mice, also offers the strongest causal evidence that age-related memory loss and Alzheimer's disease are distinct conditions.
"Our study provides compelling evidence that age-related memory loss is a syndrome in its own right, apart from Alzheimer's. In addition to the implications for the study, diagnosis, and treatment of memory disorders, these results have public health consequences," said Columbia University Medical Center (CUMC) researcher Kandel.

The hippocampus, a brain region that consists of several interconnected subregions, each with a distinct neuron population, plays a vital role in memory.
Studies have shown that Alzheimer's disease hampers memory by first acting on the entorhinal cortex (EC), a brain region that provides the major input pathways to the hippocampus, researchers said.

It was initially thought that age-related memory loss is an early manifestation of Alzheimer's, but mounting evidence suggests that it is a distinct process that affects the dentate gyrus (DG), a subregion of the hippocampus that receives direct input from the EC.
"Until now, however, no one has been able to identify specific molecular defects involved in age-related memory loss in humans," said co-senior author Scott A Small, director of the Alzheimer's Research Center at CUMC.

Researchers began by performing microarray (gene expression) analyses of postmortem brain cells from the DG of eight people, aged 33 to 88, all of whom were free of brain disease.
The analyses identified 17 candidate genes that might be related to ageing in the DG. The most significant changes occurred in a gene called RbAp48, whose expression declined steadily with ageing across the study subjects.
To determine whether RbAp48plays an active role in age-related memory loss, the researchers turned to mouse studies.
"The first question was whether RbAp48is downregulated in aged mice," said lead author Elias Pavlopoulos, associate research scientist in neuroscience at CUMC.

"And indeed, that turned out to be the case - there was a reduction of RbAp48 protein in the DG," said Pavlopoulos.
When the researchers genetically inhibited RbAp48in the brains of healthy young mice, they found the same memory loss as in aged mice, as measured by novel object recognition and water maze memory tests. When RbAp48inhibition was turned off, the mice's memory returned to normal.
The study was published in the journal Science Translational Medicine.