Brain Bank

The donation of post-mortem brain tissue for research is of fundamental importance to further understanding of the causes of these disorders and to develop more effective diagnostic tools and treatments for these conditions.

Could irritable bowel syndrome (IBS) and and mental health disorders such as anxiety be linked?

IBS affects around 1 in 10 people and causing symptoms such as abdominal pain, bloating and bowel dysfunction that can significantly affect people’s lives. Causes of IBS are not well understood but researchers have now identified several genes that provide clues into the origins of IBS.

In a large international study of more than 50,000 people with IBS, research teams from more than 40 institutions looked at genetic data from people who suffer with IBS and compared them to people without IBS (controls). The findings were repeated with de-identified data from people who have consented to research, again, people with IBS to those without.

The results showed that overall, heritability of IBS (how much your genes influence the likelihood of developing a particular condition) is quite low, indicating the importance of environmental factors such as diet, stress and patterns of behaviour that may also be shared in the family environment.

However, 6 genetic differences were more common in people with IBS than in controls. Researchers found most of the altered genes appear to have more clear-cut roles in the brain and possibly the nerves which supply the gut, rather than the gut itself.

The team also looked for overlap between susceptibility to IBS and other physical and mental health conditions.  They found that the same genetic make-up that puts people at increased risk of IBS also increases the risk for common mood and anxiety disorders such as anxiety, depression, and neuroticism, as well as insomnia. However,  this doesn’t mean that anxiety causes IBS symptoms or vice versa.

Read the full press release from November 2021.

Brain receptor uses nutritional state to control growth and age at puberty

It was previously thought growing taller and reaching sexual maturity may have been related to access to food for pregnant women and children, but researchers have now found it might be related to a receptor in the brain.

It is already known that signals reach the brain to indicate the body’s nutritional state. In a part of the brain called hypothalamus, hormones act on a small group of neurons that produce signals called melanocortins.

The melanocortins act on a variety of receptors, two of which are present in the brain. One of these, the melanocortin 4 receptor (MC4R) has previously been shown to regulate appetite and lack of MC4R results in obesity, but the MC4R system does not control the effect of nutrition on growth and timing of puberty.

Researchers found that in response to nutritional signals the MC3R system controls the release of key hormones regulating growth and sexual maturation, showing the brain can sense nutrients. This study could help people with the management in growth and puberty disorders.

Read the full press release from November 21

New study to test personalised breast cancer screening

MyPeBS trial is taking place in 6 European countries and plans to involve 85,000 volunteers aged between 50 and 70 who have never had breast cancer before.

Currently those between the ages of 50-70 are invited for a routine NHS breast cancer screening by having a mammogram every three years. However, not everyone has the same breast cancer risk, other factors such as genetics, hormones, family history and breast density can put some in a higher risk category.

The MyPeBS study randomly assigns trial volunteers to follow either the standard NHS screening schedule or a personalised screening schedule according to their risk of breast cancer.

Professor Fiona Gilbert, professor of radiology at University of Cambridge and imaging theme lead for the NIHR Cambridge Biomedical Research Centre is leading the UK study. “This is an opportunity to take part in one of the largest studies so far into how we find early stage breast cancer. By taking a saliva sample and history from those selected on the trial, we can identify whether they are at higher or lower risk of developing breast cancer. Once we know this, we can tailor screening to their own personal needs.”

Cambridge University Hospitals NHS Foundation Trust (CUH), the Leeds Teaching Hospitals NHS Trust and Manchester University NHS Foundation Trust (MFT) will be supporting the UK arm of the study and plans to recruit 10,000 volunteers which will last for 4 years. The Cambridge site will be supported by the NIHR Cambridge BRC.

For more information about the trail, go to: www.mypebs.eu

ITV News reported on the trial in October 2021 or read the full news article.

 

Identifying the cause of Alzheimer’s progression in the brain

An international research team, led by the University of Cambridge and supported by the NIHR Cambridge BRC, investigated how Alzheimer’s disease progresses in the brain.

In Alzheimer’s disease, tau and another protein called amyloid-beta, build up in clumps known as aggregates, causing brain cells to die and the brain to shrink. This results in memory loss, personality changes and difficulty carrying out daily tasks.

Alzheimer’s disease develops over years and can be hard to study the progression. Researchers looked at post-mortem brain samples from Alzheimer’s patients, as well as brain PET (positron emission tomography) scans from patients who were at different stages of the disease, from mild impairment through to those with late-stage symptoms.

It was thought that Alzheimer’s develops from one part of the brain and then spreads, but researchers found aggregates in multiple regions of the brain and that trying to stop the spread in just one part will do little to slow down the disease.

This is the first time that human data has been used to understand the development of Alzheimer’s disease over time. The findings will give researchers a better understanding of Alzheimer’s and other neurological diseases and will be able to help develop new treatments.

Read the full news story from October 2021

Markers to help newly diagnosed seropositive rheumatoid arthritis patients

Researchers collected clinical and laboratory measures from 28 UK centres every 3 months over a total of 18 months to understand the progression of seropositive rheumatoid arthritis.

It was measured against the 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) and Simplified Disease Activity Index (SDAI).

Researchers found that collecting biological markers early after diagnosis could help manage the disease.

Read the full paper published in October 2021

Positive phase 3 results reported in trial for new COVID-19 vaccine supported by Cambridge

The trial has been taking place at 22 locations across the UK and recruited a total of 4012 participants aged 18 years and over, and 660 adolescents.

Results showed in October 2021, that the vaccine was successful in producing high levels of neutralising antibodies against the COVID-19.

Developed by the French specialty vaccine company Valneva and manufactured in Scotland, the vaccine is the only inactivated, adjuvanted COVID-19 vaccine in clinical development in Europe. This means, that like flu and polio vaccines, it contains dead versions of the virus that cannot cause disease. Valneva hopes to initially get the jab approved for those aged between 18 and 55.

This national trial was supported at the Cambridge site by the NIHR Cambridge Clinical Research Facility and NIHR Cambridge BRC.

World first for AI and machine learning to treat Covid patients worldwide

In what’s known as federated learning, the research applied an algorithm to analyse anonymised electronic patient health data and chest x-rays from 10,000 Covid patients worldwide, including 250 at Addenbrooke’s Hospital.

The study – dubbed EXAM – took just two weeks of AI ‘learning’ to achieve high-quality predictions on how much extra oxygen a patient would need in the first days of hospital care.

To maintain strict patient confidentiality, the patient data was fully anonymised and an algorithm was sent to each hospital so no data was shared or left its location.

Once the algorithm had ‘learned’ from the data, the analysis was brought together to build an AI tool which could predict the oxygen needs of hospital Covid patients anywhere in the world.

This model can be used to help frontline physicians worldwide.

This is an abridged version of the article first published on our website on 15 September 2021.

Studying brain activity in Progressive Supranuclear Palsy

PSP is caused by the cells in the brain becoming damaged as a result of a build-up of a protein called tau.

Researchers looked at the brain activity patterns and found patients with PSP spend more time than individuals without the disease in certain brain states, meaning their brain activity was less flexible and less efficient than normal. The time spent in these brain states was more noticeable in participants who were more severely affected with PSP.

Researchers noticed that it wasn’t just certain parts of the brain that are most affected but it could affect the whole brain, even where it may appear normal on a scan or have no tau pathology.

Read the full paper published in July 21

Neuroinflammation predicts disease progression in PSP

Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease that can cause problems with balance, movement, vision, speech and swallowing. It occurs when brain cells become damaged from the build-up of protein called tau.

Patients with PSP volunteered for a trial which would involve having their brains scanned with a PET (Positron Emission Tomography) scan. The patients were then followed up for a few years.

Researchers were able to map where the inflammation occurred in the brain and highlight any significant changes. It could mean that using PET scans may be able to help clinicians see how PSP is progressing in their patients.

Read the full paper from March 21

Can looking at the brains communication channels help detect dementia earlier?

These connect to neurons in the brain and to the neurons in the rest of the body. Loss of these synapses is common in early dementia.

By using a PET (positron emission tomography) scan, researchers are now able to measure the amount of synapses in the brain.

Looking at healthy volunteers who are at risk of developing dementia because of a mutation in a gene called C9orf72, they found synapse loss was already present many years before symptoms were expected, especially in a part of the brain called the thalamus.

Spotting these changes early could be vital to help those who are at high risk of dementia. Patients will be able to be  monitored and begin treatment sooner.

Read the full paper from June 21

‘Biological fingerprint’ in blood could help identify COVID patients with no symptoms

This means they can identify people who have had COVID-19 even if they displayed no symptoms – and the biomarkers last several months after infection.

Current practice requires people to take a PCR test at the time of infection or an antibody test, to see if they had the virus but were asymptomatic.

As a result of the research the team has received £370,000 from the National Institute for Health Research (NIHR) to develop a COVID-19 diagnostic test that will complement existing antibody tests, as well as develop a test that could diagnose and monitor long Covid.

The research builds on a pilot project supported by the Addenbrooke’s Charitable Trust which has been recruiting patients from the Long COVID Clinic established in May 2020 at Addenbrooke’s Hospital.

During the pilot, the team recruited 85 patients to the Cambridge-led NIHR COVID BioResource, which collects blood samples from patients when they are first diagnosed and then at follow-up intervals over several months.

In their initial findings, they identified a molecule known as a cytokine produced by T cells in response to infection – which persists in the blood for a long time after infection.

By following patients for up to 18 months post-infection, the team hopes to address several questions, including whether immunity wanes over time. This will be an important part of helping understand whether people who have been vaccinated will need to receive boosters to keep them protected.

As part of their pilot study, the team also identified a biomarker found in patients with long COVID. Their work suggests these patients produce a second type of cytokine, which persists in patients with long COVID and might be useful for diagnosing long COVID and help in the development of new treatments against COVID.

This is an abridged version of the press release which was first published on our website on July 19, 2021.