February 26, 2024

Giant “Super Neurons” Discovered in SuperAger Brains

According to a brand-new study by Northwestern Medicine, neurons in an area of the brain responsible for memory were substantially bigger in SuperAgers compared to cognitively typical peers.
Post-mortem brains of SuperAgers expose significantly larger nerve cells in memory area.

Neurons in the entorhinal cortex, an area of the brain responsible for memory, were considerably larger in SuperAgers compared to cognitively typical peers and individuals with early-stage Alzheimers illness. They were even bigger compared to people 20 to 30 years more youthful than SuperAgers– who are aged 80 years and older. This is all according to a brand-new Northwestern Medicine study that was released on September 30 in The Journal of Neuroscience.
These SuperAger neurons did not harbor tau tangles, a signature trademark of Alzheimers illness.

Nerve cells in the entorhinal cortex, an area of the brain responsible for memory, were significantly larger in SuperAgers compared to cognitively typical peers and individuals with early-stage Alzheimers disease.” The exceptional observation that SuperAgers revealed bigger neurons than their more youthful peers may imply that big cells were present from birth and are maintained structurally throughout their lives,” stated lead author Tamar Gefen. Researchers examined the entorhinal cortex of the brain because it manages memory and is one of the first locations targeted by Alzheimers disease. The entorhinal cortex is comprised of 6 layers of neurons packed on top of one another. They determined the size of nerve cells in layer II of the entorhinal cortex (compared to layers III and V) of all the brains.

SuperAger nerve cells are even bigger than those in individuals 20 to 30 years more youthful
These nerve cells do not have tau tangles that are a hallmark of Alzheimers.
Bigger neurons in the brains memory region are a biological signature of SuperAging trajectory.

” The amazing observation that SuperAgers showed bigger neurons than their more youthful peers might imply that large cells were present from birth and are kept structurally throughout their lives,” said lead author Tamar Gefen. She is an 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 remarkable memory was the first research to demonstrate that these people bring a distinct biological signature that makes up larger and much healthier nerve cells in the entorhinal cortex that are relatively void of tau tangles (pathology).
The Northwestern SuperAging Research Program research studies unique individuals referred to as SuperAgers, 80+ year-olds who reveal extraordinary memory a minimum of as great as individuals 20 to 30 years their junior..
” To comprehend how and why individuals might be resistant to developing Alzheimers disease, it is very important to carefully investigate the postmortem brains of SuperAgers,” Gefen stated. “What makes SuperAgers brains unique? How can we harness their biologic characteristics to assist senior stave off Alzheimers illness?”.
Scientist investigated the entorhinal cortex of the brain because it controls memory and is one of the very first places targeted by Alzheimers illness. The entorhinal cortex is comprised of six layers of nerve cells packed on top of one another. Layer II, in particular, gets details from other memory centers and is a really particular and important center along the brains memory circuit..
In the study, the research group demonstrated that SuperAgers harbor big, healthier nerve cells in layer II of the entorhinal cortex compared to their same-aged peers, people with early phases of Alzheimers disease, and even people 20 to 30 years younger. They likewise discovered that these large layer II nerve cells were spared from the development of tau tangles..
Taken together, the findings show that a nerve cell spared from tangle development can keep its structural stability (i.e., stay large and healthy). The inverse also appears to be true: Tau tangles can cause neuronal shrinking..
Participants in the SuperAger study donate their brains for research after their death..
For the study, researchers analyzed the brains of six SuperAgers, seven cognitively typical elderly individuals, six young people, and 5 people with early stages of Alzheimers. They measured the size of neurons in layer II of the entorhinal cortex (compared to layers III and V) of all the brains. They also evaluated the existence of tau tangles in these cases..
For factors that remain unidentified, cell populations in the entorhinal cortex are selectively vulnerable to tau tangle development during typical aging and in the early stages of Alzheimers illness..
” In this study, we show that in Alzheimers, neuronal shrinkage (atrophy) in the entorhinal cortex appears to be a characteristic marker of the disease,” Gefen stated..
” We think this procedure is a function of tau tangle development in the affected cells leading to bad memory abilities in older age,” Gefen said. “Identifying this contributing factor (and every contributing element) is important to the early identification of Alzheimers, monitoring its course and assisting treatment.”.
Future research is essential to identify how and why neuronal integrity is protected in SuperAgers. Gefen wants to specifically concentrate on penetrating the cellular environment..
” What are the chemical, metabolic or genetic functions of these cells that render them resistant?” she asked. She likewise prepares to examine other hubs along the memory circuit of the brain to much better understand the spread of or resistance to illness..
” We anticipate this research study to be amplified and more impactful through a $20 million expansion of the SuperAging Initiative now enrolling five sites in the U.S. and Canada,” stated Emily Rogalski. She is the associate director of the Mesulam Center for Cognitive Neurology and Alzheimers Disease at Northwestern University Feinberg School of Medicine.
Reference: “Integrity of neuronal size in the entorhinal cortex is a biologic substrate of exceptional cognitive aging” by Caren Nassif, Allegra Kawles, Ivan Ayala, Grace Minogue, Nathan P. Gill, Robert A. Shepard, Antonia Zouridakis, Rachel Keszycki, Hui Zhang, Qinwen Mao [MD, PhD], Margaret E. Flanagan [MD], Eileen H. Bigio [MD], M.-Marsel Mesulam [MD], Emily Rogalski [PhD], Changiz Geula [PhD] and Tamar Gefen [PhD], 30 September 2022, The Journal of Neuroscience.DOI: 10.1523/ JNEUROSCI.0679-22.2022.
This research study was supported by the National Institute on Aging of the National Institutes of Health (grant numbers P30AG013854, R01AG062566, R01AG067781, R56AG045571, r01ag045571, and u19ag073153)..