We've updated our Privacy Policy to make it clearer how we use your personal data.

We use cookies to provide you with a better experience. You can read our Cookie Policy here.

Advertisement

High Brain Metabolism Could Be Early Sign of Alzheimer's

A 3D model of a human brain with coloured string emitting from the sides.
Credit: iStock.
Listen with
Speechify
0:00
Register for free to listen to this article
Thank you. Listen to this article using the player above.

Want to listen to this article for FREE?

Complete the form below to unlock access to ALL audio articles.

Read time: 2 minutes

An early phase in the process of developing Alzheimer’s disease is a metabolic increase in a part of the brain called the hippocampus, report researchers from Karolinska Institutet in a study published in Molecular Psychiatry. The discovery opens up for new potential methods of early intervention.


Alzheimer’s disease is the most common form of dementia and strikes about 20,000 people in Sweden every year. Researchers now show that a metabolic increase in the mitochondria, the cellular power plants, is an early indicator of the disease. 


The teams behind the study used mice that developed Alzheimer’s disease pathology in a similar way to humans. The increase in metabolism in young mice was followed by synaptic changes caused by disruption to the cellular recycling system (a process known as autophagy), a finding that was awarded the Nobel Prize in Physiology or Medicine in 2016.

Want more breaking news?

Subscribe to Technology Networks’ daily newsletter, delivering breaking science news straight to your inbox every day.

Subscribe for FREE

After a time, metabolism in the Alzheimer brain usually declines, which contributes to the degradation of synapses. This the researchers could also see in the older mice, which had had the disease for longer time.


“The disease starts to develop 20 years before the onset of symptoms, so it’s important to detect it early – especially given the retardant medicines that are starting to arrive,” says Per Nilsson, researcher at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet. “Metabolic changes can be a diagnostic factor in this.”


Maria Ankarcrona, researcher at the same department continues:

“Interestingly, changes in metabolism can be seen before any of the characteristic insoluble plaques have accumulated in the brain. The different energy balance tallies with what we’ve seen in images of the Alzheimer brain, but we’ve now detected these changes at an earlier stage.”


The study was conducted in close partnership between both researchers’ groups, who analysed the part of the mouse brain called the hippocampus, a structure that plays an important part in short-term memory and that is affected early in the pathological process. 

RNA sequencing was used

Applying the technique of RNA sequencing to see which genes are active in the cells of the hippocampus during different stages of the disease, the researchers discovered that one of the early stages of the disease is an increase in mitochondrial metabolism.


The researchers studied the changes that then appeared in the synapses between the brain’s neurons using electron microscopy and other techniques, and found that vesicles called autophagosomes, whereby spent proteins are broken down and their components metabolised, had accumulated in the synapses, disrupting access to functioning proteins.


The researchers will now be studying the role of mitochondria and autophagy in the development of Alzheimer’s disease in more detail – for example, in mice whose disease provides an even better model of the Alzheimer brain.


“These findings highlight the importance of retaining functional mitochondria and normal protein metabolism,” says Dr Nilsson. “Going forward, we’ll be able to do tests on mice to see if new molecules that stabilise mitochondrial and autophagic function can retard the disease.”


Reference: Naia L, Shimozawa M, Bereczki E, et al. Mitochondrial hypermetabolism precedes impaired autophagy and synaptic disorganization in App knock-in Alzheimer mouse models. Mol Psychiatry. 2023. doi: 10.1038/s41380-023-02289-4


This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.