An early phase in the process of developing Alzheimer’s disease is a metabolic increase in a part of the brain called the hippocampus, new research has revealed.
The findings open up new potential methods of early intervention.
The new research has shown a metabolic increase in the mitochondria, the cellular power plants, is an early indicator of the disease.
The researchers 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 in a process known as autophagy.
This finding was awarded the Nobel Prize in Physiology or Medicine in 2016.
Metabolism in the Alzheimer brain usually declines over time, contributing to the degradation of synapses.
The researchers could also see this in the older mice, which had had the disease for longer time.
Per Nilsson, associate professor at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, said:
“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..
“Metabolic changes can be a diagnostic factor in this.”
Maria Ankarcrona, professor at the same department, added:
“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.”
Researchers analysed the rodents’ hippocampus – an area that plays an important part in short-term memory and is affected early in the pathological process.
After applying 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 scientists 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 research team 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’s brain.
Nilsson said:
“These findings highlight the importance of retaining functional mitochondria and normal protein metabolism.
“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.”