Immune system 'plays a role in dementia'

“Scientists have identified a new cause of devastating neurological conditions,” the Mail Online reports – but this is entirely inaccurate.

A review of existing evidence makes the case that the innate immune system may be involved in neurodegenerative conditions, which are associated with progressive damage to brain cells, like Alzheimer’s and Parkinson’s. However, no new evidence was provided.

The innate immune system is designed to prevent the spread of infection by identifying foreign bodies such as viruses that may have infected cells and, if needs be, killing these cells so the infection doesn’t spread.

The review argues that the innate immune system initially activates to eliminate a perceived threat of brain cell abnormality. But by remaining active over time, it causes low-level prolonged damage to normal brain cells, ultimately leading to their death.

The idea that immune responses may play a role in dementia is nothing new. A study published earlier this year tried using immunosuppressant drugs on rats with symptoms of dementia, with some degree of success.

This review doesn’t pretend to be anything other than a collection of evidence supporting a hypothesis. It provides a useful range of evidence-based points exploring potential trigger molecules, genetic susceptibility, and how the underlying biology might work.

As any reputable scientist will tell you, a hypothesis needs to be tested by experimentation before it can advance into a credible theory.

Where did the story come from?

The review was carried out by researchers from the University of Adelaide in Australia, and was funded by the Australian National Health and Medical Research Council, and a grant from the National Ataxia Foundation.

It was published in the peer-reviewed journal, Frontiers in Neuroscience. The study is open access, so it is free to view online and download as a PDF.

The Mail Online’s headline, “Scientists discover new trigger for devastating brain diseases”, is not accurate and the quality of its reporting is poor.

The study in question was a review, meaning it brought together research already published. There is no new laboratory or human study involved here, which isn’t most people’s idea of a “discovery”. 

What kind of research was this?

This was a review of evidence to support the idea that a common disease-causing mechanism for neurodegenerative disease exists, and that “surveillance” by the innate immune system mediates cell death.

The innate immune system helps protect your body – inside and out – from threats like bacteria, viruses and cell damage. It’s like a surveillance system keeping an eye on your body.

When foreign bacteria enters your blood, when you cut yourself and have dirt in your wound, or even if some of your cells are behaving abnormally, your innate immune system kicks in to attack and destroy the threat.

This often involves mobilising the immune system to trigger abnormal cells – those possibly infected by viruses or bacteria – to self-destruct, taking the bacteria or other offending organism with it. This process is called programme cell death or, in biological vernacular, apoptosis.

The immune system has innate and acquired components, which recruit different cells and processes to detect and neutralise health threats.

The innate immune system is largely what you are born with, whereas the acquired immune system varies from person to person, depending on what sorts of bacteria, viruses and other micro-organisms you come across in your life.

What did the research involve?

The review reports no methods, only stating that the researchers intended to “present evidence to support the hypothesis that a common pathogenic mechanism for neurodegenerative disease exists, and is mediated by innate surveillance-cell death”.

As such, we cannot assume they used systematic review methodology in their search for relevant material. This means some relevant evidence may have been missed.

The review openly looked for evidence in support of one theory, so was not concerned with alternative theories or the relative strength of evidence behind each study.

What were the basic results?

The review itself describes the function of the innate immune system, how it triggers cell death and molecules for the immune system to attack, and different pathways whereby it can damage our bodies.

The researchers explain that many neurodegenerative diseases like Alzheimer’s and Parkinson’s diseases involve the gradual damage and death of brain cells called neurones.

But it isn’t clear whether many disease-specific mechanisms are involved or whether they share a common disease-causing mechanism.

The review argues there is an increasing body of evidence that suggests the innate immune system is activated across a number of neurodegenerative conditions, so might be the obvious candidate for a common underlying mechanism.

Delving more into specifics, the researchers suggest that the innate immune system is initially activated to eliminate a perceived threat of brain cell abnormality in neurodegenerative diseases.

But it cannot remove the threat, meaning the immune system remains active, causing low-level prolonged damage and, ultimately, progressive brain cell death.

The review also identifies possible genetic susceptibility markers, identifying those more likely to have a larger innate immune response to brain cell damage in this way.

A lot of research on neurodegenerative diseases has focused on disease-specific features of the disease – in Alzheimer’s, for example, the damaging bundles of amyloid protein that gather in the brain.

The review’s authors argue that while these are important, we shouldn’t ignore the possibility of a generic component across diseases, which in their view is driven by the innate immune system.

How did the researchers interpret the results?

The researchers concluded that, “Here we have assembled evidence in favour of the hypothesis that neurodegenerative disease is the cumulative result of chronic activation of the innate surveillance pathway, triggered by endogenous or environmental danger or damage associated molecular patterns in a progressively expanding cascade of inflammation, tissue damage and cell death.” 

Conclusion

This review presents evidence supporting the idea that the innate immune system is involved in a range of neurodegenerative conditions, such as Alzheimer’s and Parkinson’s.

Reviews like this are very useful at summarising the current state of science in an area, but may miss important research, unless they are systematic.

This review was openly one-sided, transparently exploring the evidence behind one hypothesis.

While there is nothing wrong with that, a more systematic and balanced review would add the extra value of being able to discuss alternative ideas and find out how much evidence stacks up behind each one, aiding comparisons. 

Despite news coverage suggesting this is a radical new theory, the idea that the immune system might be involved in neurodegenerative conditions has been around for a while.

A study from earlier this year in mice tentatively suggested that inflammation might be involved in the progression of Alzheimer’s disease, and can be reduced by targeting it. 

Any potentially promising avenue of research into neurodegenerative diseases is worth exploring, and this review provides some interesting ideas that other researchers may want to follow up. 

Links To The Headlines

Have we been getting it all wrong about dementia? Scientists discover new trigger for devastating brain diseases. Mail Online, May 13 2016

Links To Science

Richards RI, Robertson SA, O’Keefe LV, et al. The Enemy within: Innate Surveillance-Mediated Cell Death, the Common Mechanism of Neurodegenerative Disease. Frontiers in Neuroscience. Published online May 10 2016