"Could cake and chocolate lead to Alzheimer's disease?" The Daily Telegraph asks.
In a series of animal experiments, researchers attempted to see whether high blood glucose could be involved in the development of amyloid protein plaques in the brain; a characteristic hallmark of Alzheimer’s disease. These plaques are abnormal "clumps" of protein that are thought to gradually destroy healthy brain cells.
Some studies have suggested that people with high blood glucose levels and those with type 2 diabetes may be at greater risk of the disease, and this study aimed to see why that might be the case.
The experiments found that giving the mice a sugar solution over a number of hours led to an increased concentration of amyloid in the fluid surrounding the brain cells. The effect was more pronounced in older mice.
The study has only looked at the short-term effects, and not at whether high glucose levels affected longer-term plaque formation or symptoms in the mice.
At this stage, it is not conclusively proven that type 2 diabetes is a risk factor for Alzheimer’s disease, or that you have increased risk of the disease if you have a high-sugar diet.
Where did the story come from?
The study was carried out by researchers from Knight Alzheimer’s Disease Research Center and Washington University School of Medicine in the US, and was funded by the National Institutes of Health. The study was published in the peer-reviewed Journal of Clinical Investigation. It is an open-access study, so it is free to read online or download as a PDF.
The Daily Express accurately describes the methods of the study, but doesn’t make it clear until later in the research that study was on mice. The Daily Telegraph was more upfront about this fact.
The Telegraph piece also includes information on a related study into green tea and Alzheimer’s disease. We have not analysed the study, so we cannot say how accurate the Telegraph’s reporting of this study was.
What kind of research was this?
This was animal research that aimed to look into why there might be a link between blood glucose and risk of dementia, specifically Alzheimer’s disease.
The causes of Alzheimer’s disease are still not fully understood. Increasing age is the most well-established factor to date, and there is the possibility of hereditary factors. The influence of health and lifestyle factors is uncertain. Some previous studies have suggested that glucose levels in the blood may have an impact on the development of the beta-amyloid "plaques" and the tau protein "tangles" in the brain that are the hallmarks of the disease. This is supported by other studies that have suggested people with type 2 diabetes are more likely to develop Alzheimer’s disease. Therefore, this research aimed to look at whether there was a biological reason for this.
Animal studies can provide a valuable indication of how disease processes may work, but the process may not be exactly the same in humans.
What did the research involve?
The researchers carried out experiments to control the blood glucose level of a genetically engineered mouse model of Alzheimer’s disease and looked at the effect on the composition of the fluid surrounding the brain cells.
The research involved three-month-old mice, who would normally be too young to have beta-amyloid protein deposits in the brain. Under anaesthetic, the researchers gained access to the large vein and artery in the neck, and then a catheter was guided through the blood vessel into one region of the brain (the hippocampus). Once the mice were awake again, these tubes allowed the researchers to infuse glucose into the brain, and to sample the fluid around the brain cells while the mice were still awake and moving around.
In their experiments, the researchers withheld food from the mice for several hours before a glucose solution was gradually infused into the brain over four hours.
Fluid around the brain cells was sampled every hour during the infusion to look at levels of glucose, beta-amyloid protein and lactate (a compound involved with the metabolism of the brain) – the latter was used as a marker of brain cell activity. The brain was also examined after death.
Other experiments included infusing older, 18-month-old, mice that would already be expected to have some beta-amyloid build-up.
They also tried infusing different drugs to examine in more depth precisely what biological mechanisms were occurring in the brain that could be causing these effects.
What were the basic results?
In the main experiments in younger mice, the glucose infusion almost doubled glucose concentration in the brain fluid and increased the concentration of beta-amyloid by 25%. Lactate levels also increased, suggesting an increase in brain cell activity.
In the older mice, glucose infusion raised the concentration of beta-amyloid even higher – by around 45%.
How did the researchers interpret the results?
The researchers found that increased blood glucose levels affect brain cell activity glucose, leading to increased beta-amyloid in the fluid surrounding the brain cells in young mice that would normally have minimal beta-amyloid. In aged mice, the effect was even more pronounced.
They further suggest that "during the preclinical period of Alzheimer’s disease, while individuals are cognitively normal, our findings suggest that repeated episodes of transient [high blood glucose], such as those found in [type 2 diabetes], could both initiate and accelerate plaque accumulation".
This animal study supports the theory that elevated blood sugar might influence the development of beta-amyloid plaques in the brain – one of the characteristic hallmarks of Alzheimer’s disease. As the researchers say, glucose could similarly be involved in their development in humans.
However, at this stage, we cannot extrapolate these short-term results in mice much further. While animal studies provide a valuable indication of how disease processes may work in humans, the process may not be exactly the same. The study has not looked at the long-term effects of raised glucose on plaque formation in these Alzheimer’s-model mice, and how long raised levels need to be present to have an effect.
Even if the development of amyloid plaques in the human brain could be affected by levels of glucose, we don’t understand the intricacies of how this might happen or whether it can be avoided. Body cells – particularly those in the brain – need glucose, so clearly it cannot be avoided.
Currently, it has not been conclusively proven that type 2 diabetes is a risk factor for Alzheimer’s disease, or that you have increased risk of disease development by having a high-sugar diet. However, high-calorie diets are well established to be a risk factor for overweight and obesity, which are linked to many chronic health conditions, including type 2 diabetes. Sticking to current diet and activity recommendations can help to maintain good health.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
The Daily Telegraph, 6 May 2015
Daily Express, 6 May 2015
Links to the science
The Journal of Clinical Investigation. Published online May 4 2015