Alzheimer’s disease (AD) is the most common cause of dementia and affects close to 40 million people worldwide. As the condition progresses, individuals gradually lose memory, cognitive abilities, and independence. Despite decades of intensive research, there are still no treatments capable of stopping or reversing the underlying disease process.

One of the key drivers of brain dysfunction in AD is the protein tau. Under normal conditions, tau helps maintain the internal structure of neurons, supporting the transport systems that allow nerve cells to function properly. In Alzheimer’s disease, however, tau becomes abnormally modified and begins to clump together. These aggregates interfere with normal cellular transport, damage neurons, and ultimately contribute to memory impairment.

Now, an international team of scientists has identified a previously unrecognized way to protect the brain from this degeneration. Their research shows that increasing levels of the naturally occurring molecule NAD⁺ can counteract neurological damage linked to Alzheimer’s disease. The study was published in the journal Science Advances.

The collaboration was led by Associate Professor Evandro Fei Fang at the University of Oslo and Akershus University Hospital in Norway, together with Professor Oscar Junhong Luo from Jinan University in China and Associate Professor Joana M. Silva from the University of Minho in Portugal.

How NAD⁺ supports brain health
NAD⁺ (Nicotinamide adenine dinucleotide, oxidized form) is an essential molecule involved in cellular energy production and the ability of neurons to cope with stress. Levels of NAD⁺ naturally decline with age and drop even further in many neurodegenerative disorders.

“Previous research has suggested that boosting NAD⁺ using precursor compounds such as nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN) can produce beneficial effects in animal models of AD and in early-stage clinical studies. However, the biological processes responsible for these effects have remained poorly understood,” explains first author Alice Ruixue Ai.

The new study reveals that NAD⁺ works through a previously unidentified RNA-splicing pathway. This pathway is regulated by a protein called EVA1C, which plays an essential role in the process of RNA splicing. RNA splicing allows a single gene to produce multiple isoforms of a protein, and one isoform may show distinctive effects on the other isoforms. Its dysregulation is one of the most recently acknowledged risk factors for AD.