Although the definitive causes of Alzheimer’s diseases aren’t yet fully understood, one of the leading suspects is the accumulation of abnormal proteins in the brain that impinges on the activity of the neurons. Scientists at Northwestern University have explored this phenomenon in a group of elderly individuals with excellent memory, known as SuperAgers, and found them to be far more resistant to the troublesome buildup of some of these proteins, shedding further light on how the disease may take hold.
A lot of the research into the progression of Alzheimer’s focus on a pair of proteins called amyloid and tau. Clumps of amyloid are thought to build up and develop into plaques that impact on memory and cognitive function, while tau takes the form of tangles that interfere with the way nutrients are taken up by the neurons, eventually leading to the death of the cell.
The Northwestern University researchers carried out experiments to study the prevalence of these proteins in SuperAgers, a group of subjects over the age of 80 with the memory capacity of someone 20 to 30 years younger than them. These subjects are assessed annually as part of ongoing research at Northwestern’s Mesulam Center for Cognitive Neurology and Alzheimer's Disease.
The researchers analyzed the region of seven SuperAger’s brains that plays a key role in memory, called the entorhinal cortex, along with six controls of the same age. In doing so, the team found “significantly less” tau tangles in the SuperAgers than it did in the healthy controls, amounting to an almost three-fold difference in the final tally. Compared to those with Alzheimer’s, the difference was even more profound.
"This finding helps us better identify the factors that may contribute to the preservation of memory in old age," said lead study author Tamar Gefen. "This research highlighted there are gradients of vulnerability to cell death in the brain. Individuals with significant memory impairment due to Alzheimer's disease showed nearly 100 times more tangles in the entorhinal cortex compared to SuperAgers. There is a strong relationship between tau-tangles and memory loss, and these findings in a unique SuperAging cohort could guide research in a new direction."
An interesting insight from the study concerns the amyloid proteins, which were found in similar levels in the brains of the SuperAgers and the healthy controls. Like tau, these proteins are seen as key players in the progression of memory loss and Alzheimer’s, so that no difference could be found between the SuperAgers with their excellent memory and regular folks of the same age runs counter to a common school of thought.
"Many investigators have long thought that amyloid plaques are drivers of memory loss, which isn't what we found," Gefen said.
From here, the team aims to shift its focus toward the genetic and lifestyle factors that may impact one’s susceptibility to tau tangles, or how it may help them develop resistance to the harmful proteins and memory loss.
"Why are memory cells selectively vulnerable to tangles in the first place?" says Gefen."What is it about the cellular environment in the brains of SuperAgers that seem to protect them from tangles? Are the behaviors of SuperAgers somehow building up resistance in the brain?"
The research was published in the journal Cerebral Cortex.
Source: Northwestern University via EurekAlert