Brain Matters 2018 THE NEWSLETTER FROM QUEEN SQUARE BRAIN BANK FOR NEUROLOGICAL DISORDERS

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Bethany Newman
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1 Brain Matters 2018 THE NEWSLETTER FROM QUEEN SQUARE BRAIN BANK FOR NEUROLOGICAL DISORDERS

Professor Tom Warner Clinical Director of Queen Square Brain Bank welcomes you to the latest edition of Brain Matters. The last year has been an eventful one at Queen Square Brain Bank (QSBB).

Zane brings skills and experience in diagnostics and research into neurodegenerative disorders which will be a great asset to our current and future endeavours.

A publication by Dr Helen Ling and colleagues from QSBB aroused considerable interest in the national press and world media.

2 Professor Tom Warner Clinical Director of Queen Square Brain Bank welcomes you to the latest edition of Brain Matters. The last year has been an eventful one at Queen Square Brain Bank (QSBB). We were delighted to appoint Dr Zane Jaunmuktane as the new Consultant and Lecturer in Neuropathology who fills the vacancy created by the retirement of Professor Tamas Revesz. Zane brings skills and experience in diagnostics and research into neurodegenerative disorders which will be a great asset to our current and future endeavours. One ongoing research theme, chronic traumatic encephalopathy (CTE), a potential cause of dementia brought on by repeated blows to the head, has become topical in the realm of sporting injuries. A publication by Dr Helen Ling and colleagues from QSBB aroused considerable interest in the national press and world media. The group examined a collection of brains from retired professional footballers who had developed dementia in life, identifying pathological evidence of CTE in a number. This is the first study to highlight a potential link between playing football and developing chronic traumatic encephalopathy. The brain bank team are increasingly active in raising public awareness of the value of brain donation and neuroscientific research. A particularly successful new development is the Brain Day. Sixth form students interested in careers in medical science are invited to visit the QSBB to learn about our work and meet researchers and patients, culminating in meeting a brain. We intend to make this an annual event especially to allow less advantaged students the opportunity to gain insights that may inform their career choices. We are constantly looking for ways to raise money and were delighted when one of our clinical research fellows, Dr Pedro Barbosa, ran the London Marathon and raised 1000 for our funds. Most importantly I would like to express our appreciation to all the donors and families and friends for their invaluable support, without which none of our achievements would be possible. Another key publication by Principal Research Fellow, Dr Tammaryn Lashley and co-workers examined in detail for the first time several significant proteins in a group of frontotemporal dementias. The project shed new light on an area that could possibly lead to understanding how these diseases arise. Dr Zane Jaunmuktane Dr Pedro Barbosa We intend to make this an annual event especially to allow less advantaged students the opportunity to gain insights that may inform their career choices.

Research Updates Dr Juan Eugenio Iglesias, Senior Research Fellow, UCL Medical Physics and Biomedical Engineering, and Ms Shauna Crampsie, Research Technician at QSBB, are building a high-resolution

3 Research Updates Dr Juan Eugenio Iglesias, Senior Research Fellow, UCL Medical Physics and Biomedical Engineering, and Ms Shauna Crampsie, Research Technician at QSBB, are building a high-resolution map, an atlas of the human brain. The project has received funding from the European Research Council. Recent advances in magnetic resonance imaging (MRI) are providing us with increasingly detailed representations of the human brain. However, researchers still rely on outdated computer programmes to process these images which do not capitalise on the vast improvement in MRI. The main limitation of the old software is that it was built using scans acquired approximately a decade ago which cannot show brain substructures that are now identifiable with modern MRI. This is hampering progress in neuroimaging and neuroscience as many substructures consist of small regions with different connectivity and function that are not recognised at the moment, hence the need for upgraded software. In this innovative interdisciplinary project involving scientists with backgrounds in neuropathology, neuroimaging, computer science and MRI physics, we have started to build an atlas of the human brain at an unprecedented level of detail. Using MRI scanners at the National Hospital for Neurology and Neurosurgery at Queen Square, we carefully scan a donated brain for a longer period than would be possible in life, which yields 3D pictures of high resolution. The aim is to identify hundreds of brain substructures that can finally be combined into the atlas. In addition, our objective is to develop computer programmes that use the atlas to automatically analyse MRI scans of patients. The atlas and companion tools will be publicly available so that researchers worldwide can evaluate patient MRI data at a superior level of structural detail and specificity, increasing our ability to understand the complexities of the human brain both in health and in disease. Image (below, left) showing in colour the completed 3D representation of one brain structure built with MRI scan. Dr Eduardo Fernandez, Clinical Research Fellow continues to explore the effect of autonomic symptoms on people with Parkinson s disease: The autonomic system is the part of the brain, spinal cord and nerves that regulates automatic body functions such as heart rate, blood pressure, bladder and bowel control. Impairment of the autonomic nervous system (called autonomic dysfunction) can lead to symptoms such as dizziness when standing up, constipation, urinary frequency, erectile dysfunction or excessive sweating. These can be troublesome for people with Parkinson s disease (PD) and significantly affect their quality of life. Development of autonomic dysfunction in other neurodegenerative conditions is known to be associated with a poor prognosis and we were keen to investigate whether this is also the case in Parkinson s disease. By reviewing the comprehensive medical records of one hundred donors with post-mortem confirmed PD we were able to determine how quickly their illness had deteriorated and analyse information about their autonomic symptoms during life. We found that those individuals with earlier autonomic dysfunction had more severe parkinsonian difficulties and reduced survival rate. However, microscopic analysis of tissue revealed a rapid clinical course was not matched by more widespread pathology in the brain, which suggests poor prognosis may be directly related to complications of the autonomic system and not necessarily associated with a more aggressive form of PD. In our recent publication we proposed that more attention should be given to autonomic complications and that further research is needed to ascertain whether earlier symptom control with currently available drugs would improve quality of life and life expectancy.

Professor Janice Holton, Neuropathology Director, discusses Alpha-synucleinopathies twenty years of progress : Parkinson s disease (PD) does not usually run in families but a few, originating from

This year marks the 20th anniversary of the discovery that a fault or mutation in the gene synuclein (SNCA), that encodes for alphasynuclein protein, causes their condition.

4 Professor Janice Holton, Neuropathology Director, discusses Alpha-synucleinopathies twenty years of progress : Parkinson s disease (PD) does not usually run in families but a few, originating from Greece and Italy, were known to have a familial form of the illness. This year marks the 20th anniversary of the discovery that a fault or mutation in the gene synuclein (SNCA), that encodes for alphasynuclein protein, causes their condition. It was an exciting finding and quickly led to the observation that alphasynuclein protein, which is an essential component of normal nerve function, was not just important in inherited PD. It is a major ingredient of Lewy bodies, the pathological hallmark found in nerve cells in sporadic PD and dementia with Lewy bodies, and a significant constituent of glial cytoplasmic inclusions, the pathological hallmark seen in the disorder multiple system atrophy. These landmark revelations suggested there is a related group of neurodegenerative diseases, now known as alphasynucleinopathies, of which Parkinson s disease, dementia with Lewy bodies and multiple system atrophy are the most common members. Despite this great step forward in our understanding there are still no treatments available that can alter the relentless disease progression and continued research is essential. Alpha-synucleinopathies lie at the heart of much of the research undertaken at the QSBB and we have contributed many key clinical and neuropathological advances since the brain bank was established. Recently two new mutations in the SNCA gene have been described as a result of tissue made available to support large scale genetic studies. The 20th anniversary of the discovery of SNCA mutations serves as a focus for reflection, and in recognition of the importance of this finding, a number of international meetings have been arranged to review understanding of the neuropathology, clinical presentations, genetics and potential for new treatments of alpha-synucleinopathies. I am looking forward to presenting the achievements of the QSBB to the medical and scientific community. Image (below, left) shows a microscopic view of alphasynuclein staining in tissue of a donor with a SNCA mutation showing (in brown) frequent abnormal deposits in nerve cells. Dr Pedro Barbosa, Clinical Research Fellow, is undertaking a PhD focussing on the effects of anti-parkinsonian medication on the behaviour of people with Parkinson s disease: Around fourteen percent of individuals with Parkinson s disease (PD) develop problems collectively known as impulsive compulsive behaviours (ICBs). We know that the part of the brain responsible for decision making, the reward system, is hijacked by the medications used to treat the illness. This can lead to excessive use of levodopa, akin to drug addiction, and the compulsive pursuit of pleasurable activities, such as gambling, engaging in sexual practices, shopping and eating. The lack of insight that usually accompanies ICBs means that diagnosis of these problems often comes too late, when life savings may have been lost and personal relationships disrupted. For reasons currently unknown, males who have PD at a younger age are at higher risk of developing the complications. Image (above) shows a section of tissue stained with haematoxylin and eosin to assess the structure of the nucleus accumbens, the main reward processing area of the brain.

The cause is unclear and there are still no specific treatments for ICBs.

life. At QSBB we are examining tissue from donors who had been diagnosed with ICBs in a study that is the first of its kind.

Analysis of post-mortem tissue offers a unique opportunity to look into this area in detail under the microscope to confirm these findings and determine any changes that may have caused ICBs.

Cover Image shows a section of the brain stained with luxol fast blue to identify the nucleus accumbens, the focus of Dr Barbosa s project.

developing environment which requires us to advance our professional skills and keep-up-to-date with evolving histology techniques.

The moment a brain arrives we begin methodical preparation by weighing and then separating the left and right halves, called hemispheres.

5 The cause is unclear and there are still no specific treatments for ICBs. The only therapeutic option available to physicians is to reduce the drug dosage; a measure not always effective as it commonly leads to worsening of PD symptoms and consequently reduced quality of life. At QSBB we are examining tissue from donors who had been diagnosed with ICBs in a study that is the first of its kind. Brain imaging studies have already shown that overstimulation of the brain s reward centre by anti-parkinsonian medication can lead to structural changes in life. Analysis of post-mortem tissue offers a unique opportunity to look into this area in detail under the microscope to confirm these findings and determine any changes that may have caused ICBs. Our aim is to increase understanding of the pathology of these highly disabling behaviours and provide potential pathways for the development of specific treatments. Cover Image shows a section of the brain stained with luxol fast blue to identify the nucleus accumbens, the focus of Dr Barbosa s project. Contributors A day in the life of QSBB biomedical scientists, Ms Kate Strand and Mr Robert Courtney: As the brain bank s biomedical scientists we feel lucky to work in a stimulating, constantly developing environment which requires us to advance our professional skills and keep-up-to-date with evolving histology techniques. The term histology means microscopic study of tissue and cells, a vital part of diagnostic evaluation before research can take place. The moment a brain arrives we begin methodical preparation by weighing and then separating the left and right halves, called hemispheres. One half is carefully sliced, logged, flash-frozen and stored in a minus 80 degrees freezer, thus preserving tissue in as life-like state as possible, preventing cells deteriorating and optimising the value of the donation for many years to come. The remaining half is fixed in formalin for three weeks, then dissected and examined by the QSBB s neuropathologist according to a specific protocol. Embedding samples into wax blocks enables us to cut thin slices (no wider than a hair) and place them onto microscope slides. A panel of dyes and proteins is used to demonstrate different cells and structures within the brain so that pathological detail can be analysed and an accurate description of the disease formulated. Collaborating with other brain banks in the UK as part of a Medical Research Council initiative allows us to exchange information and expertise with our neuropathology peers in an effort to standardise procedures and make improvements for the future of brain banking. Contributors from left to right: (upper row) Dr Pedro Barbosa, Mr Robert Courtney, Ms Shauna Crampsie, (middle row) Dr Eduardo Fernandez, Professor Janice Holton, Dr Juan Eugenio Iglesias, (lower row) Ms Kate Strand. As well as offering technical support and teaching to clinicians, research staff and students undertaking further degrees, we have recently mentored budding scientists; students from London schools who have spent time with us as part of their work experience. We are pleased to encourage young people into science, and having spent many years of rigorous training ourselves realise encouragement along the way is needed. Even after many years working here we both still feel motivated and inspired by the work of the Queen Square Brain Bank.

We gratefully acknowledge the support of the Leonard Wolfson Experimental Neurology Centre and several other benefactors, in particular The PSP Association and the Medical Research Council.

6 Donations Brain banking Brain banking is expensive and we continue to depend entirely on charitable benefactions for our survival. The QSBB is primarily funded by donations from the Reta Lila Weston Institute of Neurological Studies. We gratefully acknowledge the support of the Leonard Wolfson Experimental Neurology Centre and several other benefactors, in particular The PSP Association and the Medical Research Council. Coordinators from left to right: Lynn Haddon, Robert Courtney and Linda Parsons Brain donation coordinators QSBB administrator, Lynn Haddon is usually the first point of contact for potential donors. She is responsible for coordinating the brain donor scheme and along with Linda Parsons, brain bank manager and Robert Courtney, senior technician, organises the safe receipt of donated brains. Lynn, Robert and Linda provide an on-call service during evenings and weekends, and liaise with relatives, hospital staff, funeral directors and couriers, to ensure the careful donation of the brain with the minimum of distress to the relatives of the deceased. The importance of controls We would like to encourage people without a neurological condition, controls to register with our donor scheme. Controls are vital in providing researchers with an understanding of the normal appearance and function of the brain, and for comparison with the diseased brain. If you would like to offer a financial donation to support our research, please visit our website or contact Lynn Haddon. Thank you again for your support. Sponsors UCL Institute of Neurology Reta Lila Weston Institute of Neurological Studies The PSP Association Medical Research Council The Michael J Fox Foundation For Parkinson s Disease European Research Council under the European Union s Horizon 2020 research and innovation programme Multiple System Atrophy Trust The Multiple System Atrophy Coalition Fund Sophia managed by the King Baudouin Foundation Leonard Wolfson Experimental Neurology Centre If you would like further information please log on to the website: Or contact Lynn Haddon on l.haddon@ucl.ac.uk

Brain Matters The newsletter from Queen Square Brain Bank for Neurological Disorders

Brain Matters The newsletter from Queen Square Brain Bank for Neurological Disorders Brain Matters 2016 The newsletter from Queen Square Brain Bank for Neurological Disorders Welcome Professor Tom Warner, Clinical Director of Queen Square Brain Bank welcomes you to the eleventh edition