Two interesting papers have been published by the Proceedings of the National Academy of Sciences (see here and here). Taken together they provide evidence which suggests that a specific region in the brain known as the default mode network is more likely to develop Alzheimer’s Disease associated pathology due to peculiarities in the way energy is produced in this region. There’s been a good write-up at the Alzheimer’s Forum on this (see here). The researchers are telling an interesting story with many twists and turns.
When we need energy to do various activities we use one of two mechanisms to get that energy. Glycolysis is the process by which glucose is broken down to produce energy. This can take place through anaerobic or aerobic means. When we suddenly sprint over a short distance we need to get energy very quickly if there isn’t much oxygen available. The term used for this type of energy release is anaerobic glycolysis. The schematic diagram below illustrates this process in which glucose is broken down through several steps releasing the energy-producing molecule ATP as well as lactic acid which leads to muscle fatigue.
In the second case, when we are jogging over a long distance, there is more time to get oxygen to the muscles and we are able to make use of another process known as aerobic glycolysis.
The process of glycolysis is linked to another important energy producing pathway known as oxidative phosphorylation. In this reaction, electrons are transferred between molecules involved in the pathway and the end result is that a large number of energy producing ATP molecules are created. This pathway is very good at creating energy.
These two processes – glycolysis and oxidative phosphorylation have been well described and are found in introductory texts in biology and physiology. The researchers in these studies were interested in aerobic glycolysis – that is the process by which glucose is broken down to produce energy in the presence of oxygen. The energy produced by oxidative phosphorylation is so great in comparison with that produced by glycolysis alone that it has often been overlooked when looking at energy use by the brain. This is just one of the ways in which the researchers have been quite innovative in these studies.
If we turn to where energy is needed in the body, we find that the brain uses approximately 20% of the body’s energy consumption. Therefore the issue of how the brain uses energy is critically important. Needless to say the methods by which the brain consumes energy are extremely complex and may involve a sophisticated interplay between the brain’s support cells – the glial cells and the neurons. In order to investigate aerobic glycolysis, the researchers used measures of glucose consumption and oxygen consumption in the brain. By calculating the expected oxygen consumption for the given glucose consumption, the researchers were able to estimate the extent of aerobic glycolysis in different parts of the brain. It was here that there is another interesting twist in the story. The researchers found that a part of the brain known as the default mode network appeared to account for more of this type of activity than other parts of the brain. The default mode network involves several regions of the brain that are active during ‘wakeful rest’. The network is characterised by a synchronous firing activity of these different regions at roughly once every ten seconds. The network is thought to be associated with introspective activities in contrast with the brain’s responses to events in the environment. Below is a diagram illustrating the default mode network at different stages of development.
There is some evidence to suggest that the plaques that build up in Alzheimer’s Disease are more likely to be found in the regions in this network. So next, the researchers turned their attention to a component of the plaques found in Alzheimer’s Disease – ABeta peptide. Using a radiolabelled isotope which shows up this peptide in the brain, the researchers used PET scans to examine both people with Alzheimer’s Disease and people with high levels of ABeta peptide in the brain but who were cognitive normal. They found that in both groups, the ABeta peptide was more likely to be found in the regions in the default mode network. Furthermore it was more likely in those people with Alzheimer’s Disease than in those without.
While it’s tempting to draw some general conclusions about what this might mean in terms of introspection and response to external events, it is far too early to do so. Indeed it is far too early to even draw conclusions about energy metabolism and Alzheimer’s Disease. The total sample size in both studies was 58 people and so really what these studies are doing is telling us about what areas in the brain are likely to be affected in Alzheimer’s Disease, which mechanisms might be making them vulnerable and how all of this might tie in with the way the brain creates and uses energy. However there is a need for further studies to reproduce these results with a larger group of people and also to test these theories in different ways to see if they stand up to close scrutiny. If these theories do stand up to close scrutiny then they will give us exciting new insights into some of the mechanisms producing Alzheimer’s Disease and offer the possibility of novel therapies based on this understanding. So this will certainly be an interesting area to follow.
Other News in Brief
Mind Hacks has a very good round up of Spike Activity here as well as coverage of the first man diagnosed with Autism who is now 77 years of age and very well travelled as well as an intriguing study using mirrors and giving valuable insights into how the brain processes visual information (mirror, bright light and dark room required). There is also a very interesting video here demonstrating the use of programmable gloves that can apparently train a person’s to use specific movements of the hand. The researcher in the video talks about how this is being used in rehabilitation and although there’s certainly a ‘wow’ factor in seeing these gloves in action this should be interpreted with the published findings particularly given the possible clinical uses discussed.
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