UCL Neurodegenerative Disease Human Tissue Resource

Diseases of the brain and spinal cord are common and affect increasing numbers of people with advancing age. Conditions like Alzheimer's (AD) and Parkinson's (PD) affect a many elderly individuals, but can also present from young adult life particularly when there is a genetic cause. The same is true for other dementias and motor neuron disease (MND). These conditions are all characterised by death of specific groups of neurons (brain cells) and are referred to as neurodegenerative diseases (NDDs). They are progressive and eventually fatal and, currently, there is no cure for these disorders and a major source of disability in the population.

Scientists and doctors are working to understand these and many other conditions, but the causes and methods for treating them require much more research. While valuable information can be obtained from animal models of disease, cells grown in a dish, and even computer simulations, there is no substitute for testing ideas in human tissue itself. Human tissue research is often a preliminary step before embarking on a clinical trial, especially for new treatments. For this reason, 'biobanks' have been developed that collect, characterize and store brain and spinal cord tissues from humans, both with and without nervous system diseases. These tissues, and associated data, are then provided to research projects that
need to study human tissue.

The goals of this proposal are several-fold. First, the current collection procedures will be greatly expanded by recruiting brain and nervous tissue donation from eight cohorts of very well studied patients with a variety of NDDs including AD and other dementias, PD, MND as well as control brains. A novel pilot study relates to Down Syndrome, a common cause of intellectual disability and early AD type dementia. We will collect brain material from embryos, fetuses, children and adults with this condition so we can understand the development of the condition in the brain over the entire lifespan. This lifespan approach can then be implemented for other NDDs particularly genetic ones.

Secondly, we need to maximize the value of the donated brain material. This includes reducing the time-gap between death of the individual and acquisition of the brain, so that the tissue is as healthy as possible for research. Many types of data need to be linked to each brain sample, to provide a rich resource for the researchers, and this includes information
from hospital notes, imaging data like MRIs, lab results, and microscope slides from the pathology department. Genetic data (the DNA sequence) is particularly valuable for research, and we will ensure that all samples undergo genetic analysis.

The third goal of this proposal is to develop a user-friendly web-based computer platform where all samples and associated clinical information are catalogued, so they can be searched by researchers who are seeking particular tissue types, diseases or stages. Working with the MRC Dementias Platform UK informatics team we will develop such a platform.

The UCL Neurodegenerative disease Human nervous tissue resource will offer a step-change in the provision of tissue for research in this area.

The overarching aim is to build on the existing resource at the Queen Square Brain Bank (QSBB) to create a world leading neurodegenerative disease tissue resource based on unique deeply phenotyped patient and control cohorts.
Goals of the Lifespan study are to: (i) expand and enhance existing CNS tissue collections at QSBB, with close linking of clinical, imaging and biomarker data, whilst
developing new living tissue, cell and post-mortem resources; (ii) improve tissue quality, especially by reducing the post-mortem interval in donated nervous system tissue; (iii) transform current resources in terms of genetic characterization providing research tissue users with detailed genetic data from the Illumina Neuro Consortium Array to identify genetic variants in neurodegenerative diseases; (iv) develop a lifespan approach for neurodevelopmental- neurodegenerative research using Down Syndrome as exemplar and provide nervous system tissue from embryonic/fetal samples through to adult. This will enable researchers to understand the intellectual disability that progresses to early-onset dementia with AD pathological features (v) deliver a single point-of-access portal supported by an integrated IT platform to allow searches of tissue and allied clinical data.
The proposal will deliver a step change in the provision of nervous system tissue for translational research into neurodegenerative conditions.