Alzheimer's disease is a progressive and permanent loss of nerve cells in the brain. The breakdown causes memory loss, functional impairment, and personality changes.
In a new study, researchers find that the age-related reduction in a specific protein may contribute to the loss of brain function in this disease.
"This study provides a new solid clue to explain why older people are more vulnerable to Alzheimer's disease, a scientific mystery that has lasted for decades," Professor Evandro Fei Fang-Stavem says, who has led the work.
Fang-Stavem, Professor of Gerontology and Neuroscience at the Department of Clinical Molecular Biology at UiO, also heads the Fang Lab with students from ten countries. Here, they research the molecular mechanisms behind aging and age-related diseases.
We all have garbage trucks in our brains
Our brains are constantly producing waste. To keep our brains healthy, these waste products must therefore be cleaned out regularly.
"We have small systems inside our cells that constantly find, package and break down damaged or unnecessary proteins and other cellular components," Fang-Stavem says. "These systems are our garbage trucks."
As a result, the proteins are broken down into amino acids that can be reused.
In scientific terms, this process is called autophagy.
In Alzheimer's disease, the garbage truck in the brain is destroyed
In Alzheimer's disease, this cleansing process does not function well, and the proteins end up accumulating and damaging the brain. This causes disruptions in the communication between the brain cells, which leads to cognitive impairment, meaning that different functions within the brain no longer work.
This is something Fang-Stavem's group has researched extensively, and now they not only know which part of the garbage truck's engine is broken, but also how to fix it.
The key protein is called ULK1.
"ULK1 is involved in starting and running the autophagy machinery-the cleansing system-ensuring that the cell stays healthy and that it has enough energy to keep itself in peak condition," Fang-Stavem explains.
He now believes that a decline in ULK1 may be one reason why the aging brain becomes more vulnerable to Alzheimer's disease.
The brain's cleansing system declines as we grow older
The study was based on a large amount of data from various human and laboratory materials, including brain fluid samples from Alzheimer's disease patients.
"Our study suggests that ULK1 acts as a central controller for the brain's cleaning and recycling system; compared to cognitive unimpaired individuals, ULK1 is reduced in blood and brain fluid from Alzheimer's disease patients," says Anne-Brita Knapskog, a Professor at the Department of Geriatric Medicine, and a co-first author.
"When ULK1 levels fall with age, this system may become less efficient, allowing Alzheimer's-related damage to build up."
While there are a few medications available that can slow the progression of Alzheimer's disease, their effects are modest. "It is therefore urgent to develop new medications and therapies," Knapskog says.
Lower ULK1 levels in brain regions which are responsible for long-term memories
The research team also examined brain fluids from cognitively healthy older people in Norway. The data show that ULK1 levels decreased over a four-year period, even in people without cognitive impairment.
"Intriguingly, ULK1 levels were significantly lower in Alzheimer's patients than in the cognitively unimpaired controls, and this reduction appeared to become more pronounced as the disease progressed," Fang-Stavem says.
The researchers also found reduced ULK1 in brain regions affected by Alzheimer's disease. This included regions responsible for processes such as creating, storing and accessing long-term memories. These regions also have implications for our self-control and attention.
A wish to develop medications
Old age is the most significant risk factor for developing Alzheimer's disease. The older a person gets, the more likely they are to develop dementia.
The global elderly population is projected to increase significantly over the next few decades, something which worries Fang-Stavem.
"By the year 2100, one in four living people will be over 65. This represents an international concern, because there are serious health and socio-economic challenges associated with aging, including Alzheimer's."
Molecules from the plant kingdom may have significance against Alzheimer's disease
Fang-Stavem's research group has been actively searching for natural molecules that can alleviate symptoms of the disease.
Among other things, they have identified two molecules from traditional Chinese medicine and found that a molecule from passion fruit might slow the development of the disease.
Fang-Stavem is now leading a phase II clinical trial in Alzheimer's disease, which is based on a pre-clinical discovery made seven years ago. Here, a natural compound found in pomegranate showed potential in reducing "brain garbage" in Alzheimer's disease.
"We're excited to move the laboratory discovery to the clinic. Our results so far are promising," Fang-Stavem says.
However, he emphasizes that more studies are needed before ULK1 can safely be used as a measurement for disease and as a target for treatment.
"Although we are cautiously optimistic that increasing the activity of ULK1 can become a new target for developing drugs against Alzheimer's, more studies are needed to validate our findings," he concludes.
International journals highlight the study
The paper is already making waves. It was selected as an article in the May issue of the leading journal Nature Ageing. Nature Reviews Neurology, another leading journal, has written an editorial on the importance of the study's findings.
"This reflects the paper's scientific importance," Fang-Stavem says.
He wishes to highlight the work of his colleagues and co-authors on the study. "I would like to share the credit with all the co-authors, especially co-first authors Dr. Jun-Ping Pan, Dr. Ping-Jie Wang, Dr. Jianying Zhang, Prof. Anne-Brita Knapskog, and Prof. Leiv Otto Watne, as well as co-corresponding author Guobing Chen", he concludes.
Reference
Pan, J. P., Wang, P. J., Zhang, J., ...& Fang, E. F. (2026). Reduced ULK1 links impaired autophagy and mitophagy to Alzheimer's disease pathology. Nature aging, 6(5), 1079-1102. https://doi.org/10.1038/s43587-026-01108-z
