Background
Ceftriaxone is an antibiotic already used to treat bacterial infections. There is evidence from previous studies that this antibiotic also has an ability to protect the brain; Ceftriaxone can restore cognition in rats with Alzheimer’s as well as altering genes related to the protein amyloid beta. This protein plays a key role in Alzheimer’s. Amyloid beta clumps together to form ‘oligomers’, and it is this form of the protein that is most toxic. Therefore, if Ceftriaxone alters amyloid beta, it may be beneficial in treating Alzheimer’s.
Why is the study important?
This study provides further evidence that Ceftriaxone could be a potential treatment for early Alzheimer’s. It aimed to determine whether the drug could have a beneficial effect on the behaviour of mice with early Alzheimer’s, as well as the amount of amyloid beta and inflammation in their brains.
It is also important as it is an example of drug repurposing. This is a relatively new approach and aims to use existing drugs for one condition to treat another disease. Because the drug is already approved and is safety tested, it can progress through clinical trials much faster.
What did the authors do and how did they do it?
In order to mimic Alzheimer’s in mice, the authors injected amyloid beta into their brains. For comparison, they also injected the other half of the mice with water. These mice do not display the symptoms of the disease. Some mice in both groups were given Ceftriaxone, whilst the remaining animals were given a placebo. It was therefore possible to compare mice mimicking Alzheimer’s that had been given Ceftriaxone to those that had not, as well as compare them to mice that did not have the disease.
They then used several behaviour tests to examine different aspects of the mice’s’ memory and assessed whether Ceftriaxone caused any improvement. These tests were mainly different forms of mazes where the mice had a certain goal. The authors also took samples of the mice’s brains to examine inflammation in certain areas.
What are the results?
It was found that Ceftriaxone improved various aspects of the mice’s memory in some of the behavioural tests. In some instances, mice with Alzheimer’s given the drug performed better than those with the placebo. In one test, the drug restored the mice’s memory to a level equivalent in those without the disease.
Whilst not seen in all areas of the brain, inflammation was lower in diseased mice that had received Ceftriaxone compared to those who had not. The regions of the brain with this decrease were the hippocampus and frontal cortex, which are both vital in memory processing.
The authors also investigated the presence of a type of cell, called microglia, that has an important role in inflammation in the brain. It was found that these cells were more active in the mice injected with amyloid beta compared to those injected with water. Interestingly, in the prefrontal cortex, this activity was decreased in mice treated with Ceftriaxone.
What do the finding mean going forward for people with the disease?
Although it is in the early stages, this study indicates that Ceftriaxone shows promise as a treatment for Alzheimer’s disease. The drug is able to target two key factors in the progression of the disease – inflammation and amyloid beta in the brain. Further studies into Ceftriaxone would be needed, primarily to elucidate how exactly it is working in the brain to produce the improvements in memory that have been seen in this study.