A team of researchers from Columbia University Medical Center (CUMC), led by Nobel laureate Eric. R. Kandel, has discovered that a deficiency of the protein RbAp48 in the hippocampus significantly contributes to age-related memory loss and believes it is reversible. The study was conducted on postmortem human brain cells and mice. It offers the strongest evidence to date that age-related memory loss and Alzheimer’s disease are two very different 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 Dr. Kandel.

Kandel is a University Professor & Kavli Professor of Brain Science, co-director of Columbia’s Mortimer B. Zuckerman Mind Brain Behavior Institute, director of the Kavli Institute for Brain Science, and senior investigator at Howard Hughes Medical Institute. He received a share of the 2000 Nobel Prize in Physiology or Medicine for his discoveries related to the molecular basis of memory.

The hippocampus is a region of the brain that has many different interconnected subregions. Each one has a distinct neuron population and plays an important role in memory. Past studies have shown that Alzheimer’s disease effects memory by acting on the entorhinal cortex first, a region of the brain that provides input pathways to the hippocampus. Initially, it was believed that memory loss was a precursor to Alzheimer’s, but evidence has been mounting against that belief.

“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, MD, the Boris and Rose Katz Professor of Neurology and Director of the Alzheimer’s Research Center at CUMC.

This recent study was designed to look for direct evidence of age-related memory loss being different from Alzheimer’s disease. Researchers began their search by performing microarray analyses on postmortem brain cells from eight people between the ages of 33 and 88 who were all free of brain disease. They identified 17 candidate genes that could be related to aging with the most significant changes occurring in the RbAp48 gene.

To determine whether or not the RbAp48 gene plays a role in age-related memory loss, the team looked at mouse studies. When they genetically inhibited RbAp48 in the brains of healthy mice, they found the very same memory loss that had been noted in aged mice. Memory was measured by novel object recognition and water maze memory tests.

These findings were published August 28 in the online edition of Science Translational Medicine.