The overall objective of the research and activities performed in this project is to advance the national donor program and secure a steady number of Amyotrophic Lateral Sclerosis (ALS and other motor neuron diseases like progressive muscular atrophy and primary lateral sclerosis; PMA.PLS) brain donors, performing autopsies with extensive neuropathological analysis, to achieve a correct post-mortem diagnosis and provide well characterized tissue to the ALS research community.
In the past 5 years the departments of Neuropathology (Amsterdam UMCU-AMC-UvA) and Neurology (UMC Utrecht) with the support of the Stichting ALS Nederland joined their forces and expertise to achieve a virtual genetic and neuropathological characterization of all collected tissues (> 300 cases ) over a period of 30 years. A large database is established, including genomic and transcriptomic datasets, in collaboration with international initiatives such as that of the New York Genome Center (NYGC) Center for Genomics of Neurodegenerative Diseases (CGND) and project MinE, which provided additional clinical-neuropathological-genetic information for a large cohort of donors.
In this application support is being requested for to move from a virtual to a real infrastructure in Amsterdam for maintenance of the combined collection and allowing the harmonized inclusion of new autopsies. State-of-the-art methods and disease-specific protocols are used to perform a systematic analysis of this prospectively collected cohort at the genetic and neuropathological level. Along with other clinicians and neuropathologists, a sampling protocol for the collaborative biorepository of ALS/MND has been established. Both tissue and accompanying genomics data will be available to the national and international ALS research community.
Ultimately, this will aid the understanding of disease trajectories, differentiation between and within diagnoses and genetic susceptibility, fitting with the implications from the research outputs, including several recent important publications using tissue of the Dutch ALS tissue bank.
In summary, this project will yield:
Aanvrager project: Amsterdam UMC, department of Neuropathology & ALS Centrum Nederland, department of Neurology