‘SuperAgers’ more resistant to memory loss, may hold key to fighting Alzheimer’s disease

CHICAGO, Ill. — Alzheimer’s is an insidious disease which robs people of their memories, their basic functions, and eventually their lives. There’s no perfect formula which can tell who will and who won’t develop dementia in old age, but a new study finds those who don’t may hold the key to stopping cognitive decline. Researchers from Northwestern University say they have discovered what they believe is the main cause of Alzheimer’s-related memory loss.

In a study of older adults who seem to have a natural resistance to memory loss, researchers find fibrous tangles in the brain appear to have a greater role in causing dementia than plaque buildup. Tangles of tau protein and the amount of amyloid plaques in the brain have both been connected to the development of Alzheimer’s disease in previous studies.

In the new report, researchers focused on the brain makeup of “SuperAgers,” people over the age of 80 who still have outstanding memories. Study authors at the Northwestern Mesulam Center for Cognitive Neurology and Alzheimer’s Disease say these individuals have a memory capacity that matches people between 20 and 30 years-old. Scans of their brains reveal SuperAgers can better resistant tau tangles from forming in the brain region controlling memory.

“The results suggest resistance to age-related tau degeneration in the cortex may be one factor contributing to preserved memory in SuperAgers,” says lead study author Tamar Gefen in a media release.

Researchers add that these tangles form in the brain structures which transport nutrients through the nerve cells. When the pathways are tangled, it disrupts communication between neurons and keeps nutrients from maintaining cell functions. That damage kills off the brain cells and leads to cognitive decline in dementia patients.

What’s special about SuperAgers?

Researchers examined the amount of amyloid plaques and tau-containing neurofibrillary tangles in seven SuperAgers; comparing those results with six cognitively healthy individuals of the same age. The team looked at the entorhinal cortex, which is primarily responsible for memory, in both groups. Despite having good brain health, normal seniors still have three times as many tau tangles in their brains in comparison to SuperAgers.

“This finding helps us better identify the factors that may contribute to the preservation of memory in old age,” adds Gefen, an assistant professor of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine. “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,” the researcher continues. “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.”

Although amyloid plaques and protein tangles both have a reputation for sparking Alzheimer’s disease, study authors note older adults without dementia carry them too. This is why the Northwestern team is looking at SuperAgers; to find out what is going right with their brains.

Plaque in the brain has no connection to memory loss after all?

Scans of SuperAger brains also arrived at one stunning conclusion, amyloid plaque doesn’t seem to affect memory as much as many scientists think. The results discovered SuperAgers had no significant differences in the density of amyloid plaque in their brains compared to normal healthy seniors.

“Many investigators have long thought that amyloid plaques are drivers of memory loss, which isn’t what we found,” Gefen reports.

The team is now hoping to explore what keeps SuperAgers from developing Alzheimer’s by looking at the donated brains of former volunteers. Examining the ties between genetics and each person’s environment and lifestyle may provide more clues in how to prevent dementia.

“Why are memory cells selectively vulnerable to tangles in the first place?” the study author asks. “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?”

“To address these questions, we can study the molecular, biochemical, and genetic components of these specific memory cells, in SuperAgers, that are typically targeted by Alzheimer’s. And, certainly, we must take their personal narratives (history, proclivities, behaviors, cultures) into account when making conclusions about their unique neuroanatomic profiles.”

The study appears in the journal Cerebral Cortex.

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