Large-scale investments in technology infrastructure for dementia research

To meet the challenge of developing treatments and technology for those living with dementia, we must be ambitious in our thinking and equip ourselves with the best tools, technology and resources. At the UK DRI, we’re committed to building initiatives and infrastructure that provide a catalyst to groundbreaking dementia research taking place across the UK.

In just our first few years, we have launched three multi-million-pound Director’s Strategic Initiatives and two Technology Platforms that will help drive scientific breakthroughs in the dementia field.

Launched in March 2020, the Multi-‘omics Atlas Project (MAP) is a £2M Directors’ initiative led by UK DRI at Imperial, which aims to create an ‘atlas’ of the brain at different stages of Alzheimer’s disease. It is the first time that UK brain tissue resources have been coordinated on such a scale to study Alzheimer’s disease pathology at every stage of the condition, and is set to rapidly improve our understanding of the processes that lead to people developing the condition.

The project is managed by Senior Scientific Project Manager, Dr Johanna Jackson, under the leadership of Centre Director, Prof Paul Matthews. The team use an unprecedented range of advanced techniques to examine tissue from eight different regions of the brain. The aim is to gain a much fuller understanding of key cell characteristics, including what influences the genes of individual cells to be expressed, and the role of proteins and other factors on their function. The data obtained is combined with information gathered from microscopic examination of the tissue, and with the medical history of each brain donor. Powerful new molecular imaging technologies are used to examine subtle but important differences in cell types and their relationships in the brain. From these data, scientists are able to develop a better understanding of how individual cells function and interact with their environment.

Find out more about the MAP from the launch news article and dedicated MAP website.

Launched in April 2021, the IPSC Platform to Model Alzheimer’s Disease Risk (IPMAR) is a major initiative led by UK DRI at Cardiff, which aims to become one of the foremost cellular model resources available to study Alzheimer’s, helping researchers worldwide explore risk factors that contribute to development of the disease.

Late-onset Alzheimer’s disease is a multifactorial and extremely complex condition. In the majority of cases, the risk of developing it is determined by thousands of small contributions from our genes, along with environmental factors such as lack of exercise. Researchers have been analysing huge genetic datasets to generate polygenic risk scores (PRS), which are a calculation of an individual’s overall risk for developing Alzheimer’s. Led by Prof Julie Williams, Centre Director from UK DRI at Cardiff, the IPMAR team are creating and validating to 60 induced pluripotent stem cell (iPSC) lines from people with high or low polygenic risk for Alzheimer’s.

These iPSCs can be transformed into nearly any cell type in the body, such as neurons or microglia (CNS-resident immune cells), and will be an invaluable resource for modelling and studying the complex biology that the disease presents. The cells and associated data will be made available to researchers across the world to allow others to use the tools to study the many aspects that contribute to late-onset Alzheimer’s disease.

Find out more about the IPMAR from the launch news article.

Launched by UK DRI at King’s in 2019, the adeno-associated virus (AAV) vector core aims to assist with the design and pre-clinical validation and clinical trials of AAV vectors capable of delivering long lasting, cost effective and safe therapies for neurodegenerative diseases.

In recent years there has been a resurgence in gene therapy efforts that is partly fuelled by the identification and understanding of new gene delivery vectors. AAV is a non-enveloped virus that can be engineered to deliver DNA to target cells, and has attracted a significant amount of attention in the field. Prof Chris Shaw, Group Leader from UK DRI at Kings, leads the team in the generation of gene therapy vectors at the UK DRI.

The team are specialists in the production of high-quality AAV, which they apply the Centre’s research into frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). They also advise UK DRI researchers across the Institute on the development, safety and efficacy testing and production of novel AAV tools.

Find out more about the adeno-associated virus platform in the launch news article.

In December 2021, Prof Shaw and the team raised $80m Series A funding for their spin-out AvaidoBioto develop treatments for Frontotemporal dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS, motor neuron disease, MND), with a view to targeting other diseases in the future.

Read about the new spin-out AvaidoBio in this news article.

A UK DRI Platform launched in January 2022, the Biomarker Factory aims to transform the early detection, diagnosis and monitoring of dementia, by facilitating the development of fluid biomarkers for research and the clinic. This includes biological signals found in the blood, paving the way for scalable, non-invasive diagnostic tests.

Biomarkers have huge potential to transform our understanding of disease and the development of therapeutics. Short for ‘biological markers’, they are a measure – or a flag – of a biological state, helping us identify and monitor healthy biological processes or, crucially, harmful changes occurring in disease. Cutting-edge technology now allows for ultrasensitive detection of biomarkers present in blood samples even in very early stages before disease symptoms present.

The lab is based on the trailblazing work of Prof Henrik Zetterberg, Group Leader at UK DRI at UCL. This high-performance analytical platform is used for fluid biomarker development, validation and measurement, and can now also be accessed as a service for other researchers across the UK and beyond.

Find out more about the UK DRI Biomarker Factory.

Established in October 2021, the UK DRI Proteomics Platform provides access to technology, instruments and expertise to enable researchers to carry out mass spectrometry-based proteomics, and take their studies to the next level.

Through a collaboration agreement with the MRC PPU at the University of Dundee, all UK DRI researchers can meet and discuss ideas with the Lead Scientist - dedicated expertise at the Platform. A wide range of experiments can then be carried out on behalf of the researchers using multiple high-end mass spectrometers available. The platform also provides informed advice on experimental design, support with bioinformatic analysis and access to UK collaborators pioneering specialist mass-spectrometry based techniques.

Connecting the researchers in Dundee with the UK DRI and applying these techniques allows us to study proteins in unprecedented detail and to measure the state of all of the proteins in a tissue at the same time, providing very powerful tools for studying neurodegenerative disease.

Read more about the Platform in this interview with Lead Scientist Dr Bethany Geary.