New research conducted by scientists at the Karolinska Institute has revealed a surprising early phase in the development of Alzheimer’s disease. The researchers found that there is a metabolic boost in the hippocampus, a region of the brain, before the formation of typical brain plaques that are associated with Alzheimer’s. This discovery could potentially serve as an early diagnostic marker for the disease.
The team studied mice that develop Alzheimer’s disease pathology in a similar way to humans. They observed an increase in mitochondrial metabolism in the young mice, followed by synaptic changes caused by disruption to the cellular recycling system. These changes in cellular recycling, known as autophagy, play a crucial role in the early development of Alzheimer’s and are associated with synaptic disruptions.
The researchers used RNA sequencing to determine which genes were active in the hippocampus during different stages of the disease. They found that one of the early stages of Alzheimer’s is an increase in mitochondrial metabolism. Further analysis using electron microscopy and other techniques revealed that autophagosomes, which break down spent proteins, had accumulated in the synapses, disrupting access to functioning proteins.
“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,” said Per Nilsson, an associate professor at the Karolinska Institute. “Metabolic changes can be a diagnostic factor in this.”
The findings of this study highlight the importance of understanding the role of mitochondria and autophagy in Alzheimer’s disease and could potentially lead to the development of new therapeutic approaches. The researchers will continue studying the role of these processes in more detail, using mice that provide an even better model of the Alzheimer’s brain.
The study was funded by grants from the Swedish Research Council, the Swedish Alzheimer’s Foundation, and the Swedish Brain Fund, as well as through private donations. The researchers have declared no conflicts of interest.
Alzheimer’s disease is the most common form of dementia and affects approximately 20,000 people in Sweden every year. Early detection and intervention are crucial for improving outcomes for individuals with the disease. The findings of this research may pave the way for timely interventions using emerging retardant medications.
Further research is needed to fully understand the relationship between metabolic changes, mitochondrial function, and the progression of Alzheimer’s disease. However, these findings provide valuable insights into the early stages of the disease and could potentially lead to improved diagnostic methods and treatment options in the future.
The study was published in Molecular Psychiatry and is freely available to read online.