The immune system – a wolf in sheep’s clothing in Alzheimer’s?

Our immune systems are vital for keeping us healthy. This complex defence mechanism is made up of an army of millions of cells circulating in the blood and patrolling in our tissues. This army is made up of ‘battalions’ of cells with slightly different roles in identifying, alerting, destroying and clearing up damage in our bodies.

The immune system is always on the look-out for new problems to deal with, but research is suggesting it may do more harm than good in Alzheimer’s.

Genetic discoveries that you helped us to fund in 2009, 2011, 2013 and 2014 identified risk genes for the Alzheimer’s, several of which play a role in regulating the immune system. These discoveries focused interest in this area and today at Alzheimer’s Association International Conference 2016, inflammation is a hot topic being discussed.

Transformational discoveries

These genetic discoveries made by UK scientists have transformed efforts to understand the role of the immune system in Alzheimer’s. In 2014, our Research Fellow Dr Rita Guerreiro at University College London linked a gene called TREM2 to a higher risk of Alzheimer’s. TREM2 regulates the behaviour of important immune cells in the brain called microglia and it’s clear here in Toronto what a huge impact that discovery has made.

There was a whole session yesterday focusing on TREM2, with researchers across the world revealing their latest findings unpicking what this gene does in Alzheimer’s. Your support has helped to change the face of dementia research across the world, and at our conference in March we awarded Dr Guerriero our first Early Career Investigator Award for her outstanding contribution to global dementia research.

Read more about Dr Guerreiro and what makes her tick.

Unpicking the detail

The race is now on to determine what aspects of the immune systems could be most important in Alzheimer’s. This detail is vital because it reveals key processes that could be targeted by new preventions or medicines.

Many studies point towards microglia as a culprit in orchestrating the damaging effect of inflammation in Alzheimer’s. Microglia play an important role in maintaining a healthy brain environment – on patrol to clean up abnormal proteins, damage or infection. Researchers believe that while microglia may have honest intentions of clearing damage from the brain in Alzheimer’s, their sustained activation can have harmful long-term effects that could make the disease worse.

A scientific team from the University of Verona added an extra layer of complexity, showing that another group of immune cells called neutrophils can also be home to amyloid plaques and may drive the negative effects of microglia.

Turning knowledge into benefits for patients

The immune system is already an active area of research, with treatments available for several immunological disorders such as rheumatoid arthritis. Could any of these treatments work for Alzheimer’s too?

At this same conference in 2014, Prof Clive Holmes from the University of Southampton presented initial promising data of the arthritis drug etanercept in people with mild-to-moderate Alzheimer’s. At this year’s conference, we heard data from a range of international studies exploring the potential to design treatments to rein in the immune system in Alzheimer’s.

This is a great example of bench-to-bedside research – where genetic research in the laboratory has opened new avenues of research that are now being translated towards potential benefits for patients.

How your donations are making a difference

In addition to these internationally-based studies, you are helping us fund a study here in the UK at the University of Southampton to develop drugs to target the immune system in Alzheimer’s. In January, we reported a breakthrough from Dr Diego Gomez-Nicola, who protected mice from memory and thinking decline by blocking an immune protein called CSF1R. Thanks to further funding through our drug discovery initiative, the Dementia Consortium, his team is now being supported in their search for drugs to hit CSF1R with the aim of slowing the development of the disease.

We’re also putting your donations to good use exploring whether the immune system could open doors to more accurate early diagnosis of diseases like Alzheimer’s and dementia with Lewy bodies. You’ve helped to support Dr Paul Edison at Imperial College London who will present new data today suggesting that he can detect inflammation in the brains of people with early memory problems using PET scans.

Read an interview with Jay Amin, whose is looking for inflammatory ‘signatures’ in the blood of people with dementia with Lewy bodies.

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