Giant "super neurons" discovered in SuperAger brains

Neurons in the entorhinal cortex, an area of the brain responsible for memory, were significantly larger in SuperAgers compared to cognitively average peers and individuals with early-stage Alzheimer's disease. They were even larger compared to individuals 20 to 30 years younger than SuperAgers — who are aged 80 years and older.

This is all according to a new Northwestern Medicine study that was recently published in The Journal of Neuroscience.

These SuperAger neurons did not harbour tau tangles, a signature hallmark 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 maintained structurally throughout their lives," said lead author Tamar Gefen. She is an assistant professor of psychiatry and behavioural 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 research to demonstrate that these individuals carry a unique biological signature that comprises larger and healthier neurons in the entorhinal cortex that are relatively void of tau tangles (pathology).

The Northwestern SuperAging Research Program studies unique individuals known as SuperAgers, 80+ year-olds who show extraordinary memory at least as good as individuals 20 to 30 years their junior.

"To understand how and why people may be resistant to developing Alzheimer’s disease, it is important to closely investigate the postmortem brains of SuperAgers," Gefen said. "What makes SuperAgers' brains unique? How can we harness their biological traits to help the elderly stave off Alzheimer's disease?"

Researchers investigated the entorhinal cortex of the brain because it controls memory and is one of the first locations targeted by Alzheimer's disease. The entorhinal cortex is comprised of six layers of neurons packed on top of one another. Layer II, in particular, receives information from other memory centres and is a very specific and crucial hub along the brain's memory circuit.

In the study, the research team demonstrated that SuperAgers harbour large, healthier neurons in layer II of the entorhinal cortex compared to their same-aged peers, people with early stages of Alzheimer’s disease, and even individuals 20 to 30 years younger. They also found that these large layer II neurons were spared from the formation of tau tangles.

Taken together, the findings indicate that a neuron spared from tangle formation can maintain its structural integrity (i.e., remain healthy and large). The inverse also appears to be true: Tau tangles can lead to neuronal shrinkage.