Self-repair switch in the brain may help reverse memory loss

Scientists may have found a new way to protect memory from the inside out. In a recent study, boosting a natural molecule helped animals with Alzheimer’s-like symptoms remember better – and corrected tiny RNA mistakes that can throw brain cells off balance.

Rather than chasing plaques or tangles, this research – led by Dr. Evandro Fei Fang at the University of Oslo (UO) and Akershus University Hospital (AUH) – looks at the cell’s own repair tools.

Strengthening those internal systems could help the brain keep its wiring clear and its memories intact.

More than 55 million people around the world live with dementia, and Alzheimer’s remains the most common form.

Measuring how brain cells responded

Researchers boosted NAD+, a molecule that fuels energy production and coordinates repair, using vitamin-like precursors in worms and mice.

The team explored how RNA messages were edited inside brain cells and tested memory with standard behavior tasks.

They tracked alternative splicing – the reshuffling of RNA pieces to make different proteins, across hundreds of genes.

In mice carrying mutant tau, the scientists counted 509 genes with altered expression. They also found that splicing patterns shifted when NAD+ was raised.

The researchers also matched lab findings to human data and samples. The same splicing signatures and a key protein change appeared in postmortem brain tissue from people with early Alzheimer’s pathology.

Memory loss in Alzheimer’s

Proteins do not come straight off the DNA assembly line. Alternative splicing – cutting and pasting RNA in different ways – lets a single gene make several protein versions with different jobs.

In large human brain cohorts, splicing errors has been tied to Alzheimer changes at autopsy, including hundreds of altered events across the cortex, as shown in a landmark study. This is not a side note – it is a recurring signature of the disease.

Tau also lies at the center of these problems. Tau, a protein that stabilizes internal nerve cell scaffolds, can misfold and clog transport inside neurons, leading to memory loss.

The new results say one upstream dial may set several downstream switches. By pushing on cellular metabolism through NAD+, the team nudged splicing machinery toward a healthier pattern.

The brain’s repair helper

Scientists focused on a brain protein called EVA1C, which helps cells read and fix their genetic instructions.

When levels of a natural molecule called NAD+ went up, the cells made a better version of EVA1C, and the usual reading mistakes linked to Alzheimer’s disease started to drop.

Lab tests showed that EVA1C works with two other helper proteins that keep cells clean and healthy. One helper, called HSP70, fixes damaged proteins. The other, BAG1, can either protect or destroy certain proteins. 

When NAD+ made EVA1C team up more with HSP70 and less with BAG1, brain cells seemed better able to handle tau, a protein that builds up and harms memory in Alzheimer’s disease.

Tracing results into human brains

The team tested this in worms and mice that develop Alzheimer’s-like brain problems. When NAD+ levels were raised, the animals’ memory and learning improved.

But when EVA1C was blocked, those improvements disappeared. This showed that EVA1C is needed for the brain boost.

Microscope images of mouse brain cells confirmed the pattern: more NAD+ meant more cooperation between EVA1C and HSP70, and less with BAG1.

In human brain samples from people with Alzheimer’s, EVA1C levels were much lower than in healthy brains, especially in areas that control memory.

What this means for treatment

Lead scientist Dr. Fei Fang said that fixing how cells process their genetic messages might be just as important as targeting brain plaques or tangles.

Raising NAD+ seems to help brain cells stay organized and healthy, which could slow memory loss.

Some human studies are already testing NAD⁺ boosters, such as nicotinamide riboside, to see if they can safely improve brain function.

If EVA1C plays the same key role in people, doctors might one day adjust these treatments for each patient. In the future, special tools could even deliver a healthy version of EVA1C directly into the brain to protect memory cells.

Slowing memory loss in humans

Animal studies can mislead. Translating results from animals into real clinical benefits for people often fails because human brains are more diverse, and the disease unfolds over decades.

The new work draws a clear mechanistic link, yet it hinges on biomarker shifts – measurable biological signals – rather than direct clinical improvements in humans.

Early trials will need to show that splicing and memory change together in the same participants.

The study is published in the journal Science Advances.

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