Early Alzheimer’s disease brain change seen

Activity changes in the hippocampus may be an early sign of Alzheimer’s disease, researchers have found.

Dr Per Nilsson of the Karolinska Institutet, Sweden, and colleagues carried out tests on mice, as they develop Alzheimer’s disease in a similar way to humans.

They used RNA sequencing to see which genes are active in the cells of the hippocampus.

During the development of the disease, a metabolic increase was observed in the hippocampus, an area of the brain that has an important role in short term memory.

Following on from this, synaptic changes were seen using electron microscopy, which were caused by disruption to autophagy, the removal of old cell components.

Details of the study appear in Molecular Psychiatry today. Dr Nilsson said: “The disease starts to develop 20 years before the onset of symptoms, so it’s important to detect it early. Metabolic changes can be a diagnostic factor in this.”

He added that this discovery “opens up potential new methods of early intervention”.

Co-author on the work, Professor Maria Ankarcrona, commented: “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.”

Dr Nilsson added: “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.”

Naia, L. et al. Mitochondrial hypermetabolism precedes impaired autophagy and synaptic disorganization in App knock-in Alzheimer mouse models. Molecular Psychiatry 1 November 2023; doi: 10.1038/s41380-023-02289-4


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