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Why early diagnosis will hold the key to tackling Alzheimer’s disease

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Would you want to know if you were going to develop Alzheimer’s disease?

There are currently no treatments to slow, stop or prevent it.

A woman cares for a patient
A woman cares for a patient

Yet 74 per cent of UK adults would want to know they had the disease before symptoms appear, according to a survey for Alzheimer’s Research UK, the Granta Park-based charity.

A third (33 per cent) would want to know two years before, while 38 per cent of people wished to know 15 years before.

The Populus survey of 2,106 people is part of the charity’s new report titled Detecting and diagnosing Alzheimer’s disease, which calls for action to improve communication about dementia, more support for research efforts into earlier diagnosis and work to prepare the NHS for future treatments.

The need is clear. In 2017, dementia overtook heart disease as the leading cause of mortality in the UK. Some 850,000 people here are living with its devastating effects.

Alzheimer’s is the most common cause, affecting six in every 10 dementia patients.

Ian Wilson, chief executive at Alzheimer’s Research UK, said: “Right now, we face the frightening reality that one in three people born today will develop dementia in their lifetime, unless we find new preventions and treatments.

“To achieve this feat, we must be diagnosing diseases like Alzheimer’s much earlier than we can today. This is a major focus for Alzheimer’s Research UK and we’re investing millions of pounds in research to make breakthroughs in this area.

“While we are making rapid progress, it’s essential that we also act now to prepare both the public and the NHS for when these groundbreaking tests become available.

Ian Wilson, chief executive of Alzheimer's Research UK. Picture: ARUK
Ian Wilson, chief executive of Alzheimer's Research UK. Picture: ARUK

“That’s why our report includes recommendations for how the NHS can support early diagnosis, and we’re urging the Department of Health and Social Care to look now at what changes need to be made to the diagnostic pathway to support access to current and future dementia treatments. With life-changing drugs on the horizon, we don’t have time to lose.”

Researchers believe early diagnosis will prove to be critical in the long-term battle against Alzheimer’s.

But at the moment it is only diagnosed when symptoms, such as memory loss, appear.

Alzheimer’s begins damaging the brain years before this point. In fact, there are signs that clumps of protein start to build up in their brain up to two decades before such symptoms occur.

Progress is being made on new diagnostic tools, however. In August 2019 researchers from Washington University School of Medicine in St Louis reported that they were able to measure levels of the Alzheimer’s protein amyloid beta in the blood using mass spectrometry and predict whether the protein had accumulated in the brain.

It offers hope that an Alzheimer’s blood test could be available within a few years.

Early diagnosis could help any future treatments to be effective - and there is hope that a new Alzheimer’s drug could at last be on the horizon.

Results of the ARUK survey and Alzheimer's statistics in Cambridgeshire and beyond. Graphic: Cambridge Independent
Results of the ARUK survey and Alzheimer's statistics in Cambridgeshire and beyond. Graphic: Cambridge Independent

Last October, US biotechnology company Biogen Inc announced that early in 2020 it will seek regulatory approval from the FDA in the United States for its experimental early Alzheimer’s therapy aducanumab.

This followed fresh analysis of data from two previously abandoned clinical trials that yielded some encouraging results.

Studying a larger dataset from the two final-stage trials of more than 3,000 patients, where some patients were treated with the highest dose of aducanumab, showed what Biogen said was a statistically significant slowing of the decline in cognitive ability and basic activities.

Principal investigator Dr Anton Porsteinsson, director of the University of Rochester Alzheimer’s Disease Care, Research and Education Program (AD-CARE), said: “This large dataset represents the first time a phase III study has demonstrated that clearance of aggregated amyloid beta can reduce the clinical decline of Alzheimer’s disease, providing new hope for the medical community, the patients, and their families.”

If approved, it would be the first new Alzheimer’s drug in more than 15 years.

Closer to home, Mission Therapeutics – which has R&D facilities at Babraham Research Campus and offices at Granta Park – announced in December that several enzymes had been identified as potential drugs for new Alzheimer’s and Parkinson’s disease drugs, as part of its collaboration with global biopharmaceutical company AbbVie.

The companies aim to modulate specific deubiquitylating enzymes (DUBs) within the brain to enhance their ability to degrade the toxic misfolding proteins associated with neurodegenerative diseases.

Amyloid plaques on axons of neurons affected by Alzheimer's disease
Amyloid plaques on axons of neurons affected by Alzheimer's disease

In 2018, University of Cambridge scientists, working with Lund University in Sweden, reported that they had found a method to develop compounds systematically to target toxic protein oligomers in the brain.

A spin-out company, Wren Therapeutics, completed an £18million Series A financing round to help it advance its pipeline of potential drugs.

It is just one example of Cambridge taking the fight to Alzheimer’s. The university is also home to one of the UK Dementia Research Institute centres.

Among its aims is understanding the initial spreading of misfolded proteins in patients.

Two types of protein aggregates are found in the brains of those who have died from Alzheimer’s – plaques and tangles.

Plaques are caused by the clumping together of beta-amyloid protein pieces outside nerve cells, which block cell-to-cell signalling.

Tangles are found inside the nerve cells and occur when tau protein assembles into clusters of filaments and becomes insoluble.

Outside the university, Dr Michel Goedert, at the MRC Laboratory of Molecular Biology (LMB), is studying the role of tau assembly into amyloid filaments in Alzheimer’s disease and other tauopathies.

The formation of abundant tau filaments in the brain correlates with the presence of disease symptoms.

Michel Goedert, from the MRC Laboratory of Molecular Biology in Cambridge. Picture: Keith Heppell
Michel Goedert, from the MRC Laboratory of Molecular Biology in Cambridge. Picture: Keith Heppell

Together with Dr Sjors Scheres, also at the LMB, he has determined the structures of tau filaments in Alzheimer’s disease and related dementias. Dr Goedert believes that learning to predict who will get Alzheimer’s disease and preventing it from developing is our best hope of efficiently tackling this and other neurodegenerative diseases.

He told the Cambridge Independent: “Identifying people at risk of developing disease at a point when they have no symptoms, but have some of these pathologies in the brain is crucial. This requires the development of specific biomarkers, in addition to the availability of compounds that can prevent the propagation of toxic protein assemblies.”

Alzheimer’s Research UK, which conducted its survey with pharmaceutical company MSD, found widespread willingness among people to take diagnostic tests.

At least 75 per cent would be willing to undertake cognitive tests, brain imaging, blood tests and eye tests if these could help identify their risk of Alzheimer’s. And 40 per cent would be willing to have cerebrospinal fluid sampling.

Yet more than half (51 per cent) did not realise Alzheimer’s begins decades before symptoms emerge.

The charity concluded that the NHS and doctors need to help shape public understanding as tests become available, and better inform the public about early detection and diagnosis.

An Alzheimer’s Research UK map showing the prevalence of dementia across the UK - darker areas indicate higher concentrations of patients
An Alzheimer’s Research UK map showing the prevalence of dementia across the UK - darker areas indicate higher concentrations of patients

Prof Jonathan Schott, chief medical officer at Alzheimer’s Research UK and clinical neurologist at the UCL Queen Square Institute of Neurology, said: “For many people dementia, which is most commonly caused by Alzheimer’s disease, is the most feared health condition. This can make it hard to start the important conversation about why we might want to start diagnosing Alzheimer’s early.

“But this challenge is one we must overcome. Research suggests that our best shot at bringing about life-changing treatments and transforming the outlook for people with dementia may start by picking up diseases like Alzheimer’s very early, and perhaps even before symptoms start.

“These efforts are particularly timely in light of recent preliminary but encouraging results from clinical trials of new treatments in people with early stage Alzheimer’s.

“It’s vital that we begin discussions with the public about why and how we can start to make an earlier diagnosis of Alzheimer’s.

“This report suggests that the public is ready for this discussion – and that clinicians have a vital role to play.”

Read more

Winner of Brain Prize 2018, Prof Michel Goedert, on our best hope for tackling Alzheimer’s disease

Dr Michel Goedert wins $250,000 Rainwater Prize for neurodegenerative disease research at MRC LMB

Rising star Dr Ben Falcon at MRC LMB explores role of tau in dementia

How Professor Giovanna Mallucci will lead Cambridge fight against dementia

The Cambridge scientists who dominated the 2019 Alzheimer's Research UK awards

Alzheimer's breakthrough from University of Cambridge scientists ‘could lead to drug trials in two years’

Mission Therapeutics confirms potential Alzheimer’s and Parkinson’s targets with AbbVie

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