How is a brain with a good memory different from yours?

Autopsy results of the brains of "super-agers" showed that the number of neurons in their memory areas was far greater than that of ordinary people.

Source | Northwestern University

Translation | Xiong Yin

Proofreading | Erqi

In the human brain, the entorhinal cortex is responsible for the brain's memory. Recently, a new study from Northwestern University School of Medicine showed that the neurons in the entorhinal cortex of "SuperAgers" over 80 years old are much larger than those of their peers with average cognitive levels or patients with early Alzheimer's disease. Even compared with those middle-aged and elderly people in their 50s and 60s, the neurons of "SuperAgers" are the best in terms of morphology and size.

More importantly, no tau tangles, a hallmark of Alzheimer's disease, were found in these neurons of the "super-agers".

"The observation that SuperAgers have neurons that are larger than those of younger adults is striking because it suggests that neuronal size is something that is hardwired into us and that this cellular structure persists throughout our lives," said Tamar Gefen, assistant professor of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine and lead author of the study. "This suggests that larger neurons may be a biological signature of SuperAgers as they age."

Image source: Unsplash

"Super Old Man"

"Super-Agers" have outstanding memory: they are over 80 years old, but their memory is comparable to that of healthy middle-aged and elderly people in their 50s and 60s, or even better. This study revealed for the first time the biological characteristics of "super-Agers" that are different from ordinary people: their entorhinal cortex neurons are larger and healthier. From a pathological point of view, these neurons are less likely to form tau protein tangles.

The related paper was published in The Journal of Neuroscience on September 30.

"It is critical to carefully examine the autopsy results of the 'super-agers' brains, as they may reveal why some groups are spared from Alzheimer's disease," said Jeffen. "What shapes the 'super-agers' 'super-brains'? And how can we use their biological characteristics to help other elderly groups escape the suffering of Alzheimer's disease?"

Protein Tangles

Scientists studied the entorhinal cortex, which is responsible for memory and is also the first site to be affected by Alzheimer's disease. The entorhinal cortex is composed of six layers of neurons, of which the second layer of neurons is responsible for receiving information from other memory centers and is a key hub in the brain's memory circuit.

In this study, Jaffen and his colleagues found that the layer II neurons in the entorhinal cortex of the "super-agers" were larger and healthier than those of healthy peers, patients with early Alzheimer's disease, and younger individuals in their 50s and 60s. In addition, the study showed that these larger layer II neurons did not have tau protein tangles.

In summary, the study found that neurons without tangles maintained their structural integrity and were larger and healthier, while tau tangles caused neurons to shrink.

Image source: Unsplash

The name of this research topic is "SuperAgeing", and the "superagers" who serve as the research subjects donated their brains.

In the study, the scientists examined the brains of six "superagers," seven older adults with average cognitive abilities, six younger people, and five people with early Alzheimer's disease, and measured the size of neurons in layer 2 of the entorhinal cortex, compared to neurons in layer 3 and layer 5. In addition, the researchers assessed the presence of tau tangles in these cases.

For unknown reasons, populations of cells in the entorhinal cortex are particularly prone to forming tau tangles, both during natural aging and in the early stages of Alzheimer's disease.

"In this study, we show that atrophy of neurons in the entorhinal cortex may be a hallmark of Alzheimer's disease," said Jaffen.

"We speculate," Jaffen added, "that the formation of tau tangles triggers neuronal atrophy and further leads to memory loss in the elderly. It is critical to identify the causes of these various diseases, which are crucial for the early diagnosis of Alzheimer's disease, monitoring of disease progression and guiding clinical treatment."

How can "super-agers" maintain the youthful vitality of their neurons? This question needs to be answered in future research. To this end, Jaffen hopes to use the environment of the cell cycle as a foothold for exploring this issue.

Jaffen wants to focus on the question: "What chemical, metabolic or genetic features in these cells allow them to remain 'forever young'?" In addition, she plans to explore other hubs in the brain's memory circuits to better understand the progression of Alzheimer's disease and how to intervene.

"With the addition of $20 million in funding, we're looking to expand the SuperAger program to include five sites in the U.S. and Canada," said Emily Rogalski, associate director of the Mesulam Center for Cognitive Neurology and Alzheimer's Disease at Northwestern University Feinberg School of Medicine.

Cover source: Unsplash

Original link:

https://www.eurekalert.org/news-releases/966316

Paper link:

https://www.jneurosci.org/content/early/2022/09/26/JNEUROSCI.0679-22.2022