Summary: Neurons in the memory-associated entorhinal cortex of super-old people are significantly larger than their average cognitive peers, those with MCI, and even in people up to 30 years younger. Moreover, these neurons did not contain any signs of Tau, a hallmark of Alzheimer’s disease.
Source: Northwestern University
Neurons in an area of the brain responsible for memory (known as the entorhinal cortex) were significantly larger in SuperAgers compared to their average cognitive peers, people with early-stage Alzheimer’s disease, and even people 20 to 30 years younger than SuperAgers – who are 80 years and older, reports a new study from Northwestern Medicine.
These neurons did not harbor tau tangles, a hallmark feature of Alzheimer’s disease.
“The remarkable observation that SuperAgers showed larger neurons than their younger peers may imply that large cells were present from birth and are structurally maintained throughout life,” said lead author Tamar Gefen. , assistant professor of psychiatry and behavioral sciences at Northwestern University Feinberg School. of Medicine.
“We conclude that larger neurons are a biological signature of the SuperAging trajectory.”
The study of SuperAgers with exceptional memory was the first to show that these individuals carry a unique biological signature that includes larger, healthier neurons in the entorhinal cortex that are relatively free of tau tangles (pathology).
The study will be published on September 30 in The Journal of Neuroscience.
The Northwestern SuperAging research program studies unique individuals known as SuperAgers, people over the age of 80 who demonstrate exceptional memory at least as good as individuals 20 to 30 years younger than them.
“To understand how and why people may be resistant to developing Alzheimer’s disease, it is important to closely study the postmortem brains of SuperAgers,” Gefen said. “What makes the brains of SuperAgers unique? How can we harness their biological traits to help older adults ward off Alzheimer’s disease?”
Scientists have studied the entorhinal cortex of the brain because it controls memory and is one of the first places targeted by Alzheimer’s disease. The entorhinal cortex comprises six layers of neurons stacked on top of each other. Layer II, in particular, receives information from other memory centers and is a very specific and crucial hub along the brain’s memory circuitry.
In the study, the scientists show that SuperAgers harbor healthier large neurons in layer II of the entorhinal cortex compared to their age-matched peers, people in the early stages of Alzheimer’s disease, and even people in their 20s. 30 years younger. They also showed that these large layer II neurons were spared from the formation of tau tangles.
Taken together, the results suggest that a neuron spared from forming tangles can maintain its structural integrity (i.e. remain healthy and large). The reverse also appears to be true: Tau tangles can lead to neural shrinkage.
Participants in the SuperAger study donate their brains to research.
For the study, the scientists examined the brains of six SuperAgers, seven cognitively average elderly people, six young people and five people in the early stages of Alzheimer’s disease. Next, they measured the size of neurons in layer II of the entorhinal cortex (compared to layers III and V). They also measured the presence of tau tangles in these cases.
For reasons that remain unknown, cell populations in the entorhinal cortex are selectively vulnerable to the formation of tau tangles during normal aging and in the early stages of Alzheimer’s disease.
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“In this study, we show that in Alzheimer’s disease, neuronal shrinkage (atrophy) in the entorhinal cortex appears to be a hallmark marker of the disease,” Gefen said.
“We suspect that this process is a function of the formation of tau tangles in affected cells, leading to poor memory abilities in older people,” Gefen said. “Identifying this contributing factor (and each contributing factor) is crucial for early identification of Alzheimer’s disease, monitoring its course, and guiding treatment.”
Future studies are needed to understand how and why neuronal integrity is preserved in SuperAgers. Gefen wants to focus on exploring the cellular environment.
“What are the chemical, metabolic or genetic characteristics of these cells that make them resistant? she asked. She also plans to study other centers along the brain’s memory circuitry to better understand disease spread or resistance.
“We expect this research to be amplified and more impactful through a $20 million expansion of the SuperAging Initiative which now recruits five sites in the United States 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.
Funding: This study was supported by the National Institute on Aging of the National Institutes of Health (grant numbers P30AG013854, R01AG062566, R01AG067781, R01AG045571, R56AG045571, and U19AG073153).
About this superager neuroscience research news
Author: Marla Paul
Source: Northwestern University
Contact: Marla Paul – Northwestern University
Image: Image is in public domain
Original research: The findings will appear in Journal of Neuroscience
