Dear all, Upon inheriting the Looking Glass from our predecessors, we identified a number of key issues. Firstly, there were simply not enough articles being published, due both to a lack of submissions from the school community and limited responsiveness from the previous Academic Team. Secondly, the Looking Glass had not been advertised or explained effectively enough to the wider school community. As a result, we plan to implement a more consistent and engaging stream of articles on the Looking Glass. As part of this initiative, we are looking to recruit a select group of keen writers from across the lower school who would be willing to produce one high-quality piece of writing, discussion, or media each month for publication on the Looking Glass. We believe this will be hugely beneficial both to the school community, which will gain access to a wider range of opinions and viewpoints, and to prospective writers, who will be able to reference their experience contributing to the Look...
JAMIE BARRETT
Accounting for around 60% to 70% of cases of dementia, Alzheimer’s disease causes apathy and progressive loss of memory and cognitive function in later life. An estimated 50 million people worldwide have the disease, and in ageing populations this number will continue to rise, so there has been significant investment in this research topic. This has uncovered two unusual suspects that may allow us to treat the condition: the common herpes virus and bacteria that infect the gums.
Early dementia research involved examining brain tissue after death. This linked Alzheimer’s to buildups of two proteins, known as tau and amyloid, in the brain. Deposits of tau create threads that join together and tangle up between neurons while deposits of amyloid clump together among cells to form plaques. In 1984, this gave rise to the amyloid hypothesis, which suggests that these protein deposits directly cause Alzheimer’s.
Subsequently, in the 1990s, large investments were made to develop drugs to prevent these protein deposits building up - the US National Institutes of Health spent $1.9 billion on Alzheimer’s research in 2018 alone. However, 99% of the drugs that were developed didn’t pass trials, largely because they were ineffective.
This led to doubts about the amyloid hypothesis. Alongside the failure of drugs, it was found that some people could have plaque and tangles in their brain but have an exceptional memory and no signs of dementia. Reviewing the research, Bryce Vissel at the University of Technology Sydney commented, saying “there isn’t enough evidence to support the idea that amyloid has a central or unique role in Alzheimer’s”.
As well as amyloid and tau, bacteria have been discovered in the brains of people who died with Alzheimer’s, although it wasn’t clear whether the bacteria caused the disease or found it easier to enter a brain afflicted with the disease. The link was reinforced by a study in 2016 which showed that amyloid can act as an antimicrobial defense. When bacteria were injected into the brains of mice, sticky amyloid plaques formed around the bacteria in response to the infection, trapping and killing them.
At that time, gum disease was a known risk factor for Alzheimer’s, so scientists turned to the main bacterium which causes gum disease, Porphyromonas gingivalis, to reveal whether or not bacteria cause this condition. Experiments found that P. gingivalis actively invades brain regions affected by Alzheimer’s; that gum disease can make symptoms in mice worsen; and that healthy mice exposed to the bacterium can develop inflammation and neural damage typical of Alzheimer’s.
Later studies by pharmaceutical firm Cortexyme and several universities confirmed that P. gingivalis uses toxic enzymes called gingipains to feed on human tissue in the hippocampus, which plays an important role in memory. The team then looked for DNA in three Alzheimer’s brains and discovered the bacterium’s genetic material in the cerebral cortex, which is involved in conceptual thinking, of all three.
As Alzheimer’s is such a complex disease, researchers like Vissel warned that P. gingivalis may not be the only pathogen which damages brain tissue, and amyloid plaques could be protecting against viruses as well as bacteria. This warning materialised in a recent study on the common herpes virus, Herpes simplex virus-1 (HSV-1), which causes cold sores and stays in the body for life.
People with HSV-1 have a higher risk of getting Alzheimer’s, and high levels of the virus have been found in the brains of those with the condition. In order to understand how the virus might cause Alzheimer’s, Dana Cairns at Tufts University in Massachusetts and her colleagues made miniature human brains using doughnut-shaped casts of human stem cells, then coaxed them into forming brain cells. Finally, they added HSV-1 to the resulting clumps of brain tissue.
Three days later, large plaques similar to those in the brains of people with Alzheimer’s developed in the mini-brains. Other signs of Alzheimer’s like inflammation and loss of brain cells were also seen. When the quasi-brains were treated with valacyclovir, a drug used against herpes, some of this damage was reversed. This finding has led to an ongoing trial in the US that is testing whether patients with both Alzheimer’s disease and HSV-1 can be treated with valacyclovir.
Unlike Alzheimer’s, treatments already exist for HSV-1 and P. gingivalis. By gaining a better understanding of the causes of dementia, we may soon be in a position where we can prevent or treat the majority of cases.
Bibliography
NewScientist (2019), We may finally know what causes Alzheimer’s - and how to stop it. Available at: https://www.newscientist.com/article/2191814-we-may-finally-know-what-causes-alzheimers-and-how-to-stop-it/ (Accessed: 24 June 2020)
NewScientist (2020), Common herpes virus causes signs of Alzheimer’s disease in brain cells. Available at: https://www.newscientist.com/article/2242749-common-herpes-virus-causes-signs-of-alzheimers-disease-in-brain-cells/ (Accessed: 24 June 2020)
STAT (2020), Study using human brain tissue show herpes link to Alzheimer’s. Available at: https://www.statnews.com/2020/05/06/researchers-show-herpes-link-to-alzheimers/ (Accessed: 24 June 2020)
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