People with Alzheimer’s experience their first symptoms many years after the disease has begun to damage their brain, so detecting its presence early would help prevent or delay cognitive decline. Now, scientists at the Karolinska Institute in Sweden have discovered that in an early phase of this dementia there is a metabolic increase in a part of the brain called the hippocampus, directly involved in short-term memory. The study has been published in Molecular Psychiatry and may contribute to the creation of new early intervention methods.
“The disease begins to develop 20 years before the appearance of symptoms, so it is important to detect it early, especially given the slowing medications that are beginning to arrive,” stated Per Nilsson, researcher at the Department of Neurobiology, Care Sciences and Karolinska Institutet Society, which adds that “metabolic changes may be a diagnostic factor for this.”
The researchers conducted their trials with mice that developed Alzheimer’s symptoms similar to those experienced by humans. The increase in metabolism in young mice was followed by synaptic changes caused by the alteration of the cellular recycling system – known as autophagy – a finding that was awarded the Nobel Prize in Physiology or Medicine in 2016.
“Changes in metabolism can be seen before any of the insoluble plaques associated with Alzheimer’s have accumulated in the brain.”
Over time, metabolism in the Alzheimer’s brain often declines, contributing to the degradation of synapses, something they also observed in older mice, which had had the disease for longer. “Interestingly, changes in metabolism can be seen before any of the characteristic insoluble plaques have accumulated in the brain. The different energy balance coincides with what we have seen in images of the Alzheimer’s brain, but now we have detected these changes at an earlier stage,” explained Maria Ankarcrona, a researcher in the same department.
The area of the brain involved in short-term memory, the most affected
The team of scientists analyzed the hippocampus of the mice, an area of the brain that plays a fundamental role in short-term memory and that is affected from the beginning of the pathological process. The researchers used RNA sequencing to see which genes are active in hippocampal cells during different stages of the disease, and discovered that one of the first stages of the disease is an increase in mitochondrial metabolism.
These scientists studied the changes that later appeared in the synapses between brain neurons using electron microscopy and other techniques, and found that vesicles called autophagosomes, by which spent proteins are broken down and their components metabolized, had accumulated at the synapses. , disrupting access to proteins that worked.
These findings highlight the importance of maintaining functional mitochondria and normal protein metabolism, says Dr. Nilsson. “From now on, we will be able to test in mice to see if new molecules that stabilize mitochondrial and autophagic function can delay the disease.”
