Why do some people keep a sharp memory well into old age while others slide into decline? A team at Mass General Brigham in Boston thinks part of the answer could lie in a little-known enzyme that the brain apparently switches on as it gets older. Nature Neuroscience carried the paper this week.
The molecule is called PLA2G2F. It belongs to the phospholipases, enzymes that break down fats, and is released by cells into their surroundings. Until now nobody knew what it did in the brain. The researchers led by Amar Sahay and Cinzia Vicidomini stumbled on it while searching for genes that react when synapses in the hippocampus, the brain’s memory hub, are lost.
Experiments in mice then pointed to a protective role. Animals without the gene aged badly: their brains showed more inflammation, fewer synaptic connections, fatty deposits in neurons and immune cells, and weaker spatial memory by middle age. Mice given extra doses of the enzyme fared better. Boosting it in middle-aged animals, before serious problems began, even changed how their memory developed later on.
Human data fit the picture. Activity of the gene rises with age, and in tissue from deceased donors who had been tested before death it was highest in so-called resilient people, whose thinking stayed intact despite the amyloid plaques typical of Alzheimer’s disease. In human microglia, the brain’s immune cells, more enzyme meant fewer lipid droplets.
Sahay describes the enzyme as a kind of built-in counterweight that helps the brain resist decline. Outside experts are impressed by the approach, though the human evidence so far rests on a small number of brains.
Any therapy is still a long way off. The team says it is now looking for safe ways to raise the enzyme’s levels in ageing brains.
