The ‘Lewy Body Dementia Center Without Walls’ (LBD CWOW) is a cross-institutional and multidisciplinary research programme comprised of 10 international labs, led by director Dennis Dickson (MD at the Mayo Clinic) and co-director Pamela McLean, PhD (Mayo Clinic). Over five years, the centres will work together to analyse and characterise human brain tissue from LBD patients, providing novel insight into the structural characteristics of disease and reveal mechanisms that contribute to aetiology. It is the hope that this will lead to a better understanding of disease progression and pave the way for the development of therapeutics.
Lewy Body Dementia is characterised by the aggregation of alpha-synuclein (α-syn) into ‘clumps’ known as Lewy bodies. Common to other neurodegenerative disorders, proteinaceous aggregates and/or the mechanism behind their formation, is thought be a central event in disease progression. People with LBD often also have a build-up of another protein, amyloid beta (Aβ), a protein typically associated with Alzheimer’s disease. As the relationship between α-syn and Aβ is not well understood, the major focus of LBD CWOW is to understand this interaction and determine how genetic risk factors such as apolipoprotein E ε4 allele contribute to LBD pathogenesis. Using well-characterised post-mortem brain tissue from the Mayo Clinic Brain Bank the projects will probe genetics, transcriptomics, proteomics, lipidomics, structure, biochemistry, and function of Aβ and α-syn species in LBD.
As part of this $14M award, Tim’s share of $600K will be used to investigate the structural biology and biochemistry of LBD. He will utilise innovative methods to assess the load and distribution of α-syn and Aβ subspecies, using over 500 brain samples from the brain bank. Analysing their characteristics in detail, including size, structure, interactions and coexistence in select brain regions, will enable new insight into the crosstalk between α-syn and Aβ. It is hoped this will further future research efforts, identify drug targets and aid in the development of intervention strategies that may not only prevent onset, but also provide clinically relevant, symptomatic benefits to patients with LBD.
Dr Tim Bartels, said:
“This will be an unprecedented push into Lewy body Dementia research, a disease that has not gotten enough attention. Characterising disease associated changes in human samples we will be able to directly identify novel drug targets and biomarkers. The direct concerted effort of 10 highly specialised laboratories with complementary expertise and constant data exchange will ensure synergy, focus and reproducibility. All this information will be made public to help clinicians, pharmaceutical companies and basic research labs to better target their research and treatment.”
The 10 labs in the LBD CWOW include:
- Lipidomics and Proteomics studies: Junmin Peng, PhD (St. Jude, Tennessee), Xianlin Han, PhD (UTHSCSA, Texas) and John Fryer, PhD (Mayo Clinic, Florida).
- Genetics, biostatistics and network analysis: Rui Chang, PhD (Arizona University) and Owen Ross, PhD (Mayo Clinic, Florida).
- Structural biology and biochemistry: Anthony Fitzpatrick, PhD (Columbia, New York) and Tim Bartels, PhD (UK DRI at UCL, London)
- Molecular and cellular biology: Pamela McLean, PhD (Mayo Clinic, Florida), Wolfdieter Springer, PhD (Mayo Clinic, Florida), and Guojun Bu, PhD (Mayo Clinic, Florida)
- Pathological characterisation: Dennis Dickson, MD (Mayo Clinic, Florida)
- In addition, there will be an administrative core ensuring central data collection and exchange between the different labs.
Tim will be working closely with Columbia University with work due to start July 2019.