Typical age-related forgetfulness and Alzheimer's disease follow distinct courses involving different neural circuits. Not much is yet known about natural, age-related memory loss.
In a Science Translational Medicine article, Memory Protein Fades With Age, researches reported on a gene that reduced its expression by about 50% with age in both human and rodent tissues. The gene codes for a protein, called RbAp48, which regulates gene expression in the dentate gyrus, a region of the hippocampus. The dentate gyrus is involved in normal memory decline. A separate region of the hippocampus, the point of onset for Alzheimer's disease, showed no differences in the expression of RbAp48.
The protein RbAp48 might play a role in the functioning of synapses between neurons that faciliate learning and memory. It is not known why its production declines with age.
Exercise has been shown to improve the function of the dentate gyrus and to slow memory loss.
Source: Memory Protein Fades With Age
Commentary by Elizabeth Lopatto, Bloomberg:
Age-related forgetfulness may be due to a deficiency in a brain protein that helps form memories, a study found. Targeting the gene that produces that protein could lead to new therapies, the researchers said.
Scientists identified the protein, called RbAp48, in human brain cells and showed that inhibiting it in mice made the animals forgetful while raising the protein improved their memories. That suggests that age-related memory loss may be reversible, researchers said.
“All of us are living longer, and we want to stay engaged in a cognitively complex world,” said Scott Small, a study author and neurologist at Columbia University in New York. The mouse studies show that that too little of the protein is causing memory loss, he said.
The researchers took the postmortem brains of eight people ages 33 to 88 who were disease-free, and examined the function of 17 genes in a part of the hippocampus, an area that is involved in memory. That section, called the dentate gyrus, has been shown before to change with age. The strongest changes were found in a gene that expressed RbAp48, which declines in function as brains age.