The Department of Veterans Affairs Biorepository Brain Bank: A national resource for amyotrophic lateral sclerosis research

Abstract

Our objective was to describe a unique national resource to facilitate amyotrophic lateral sclerosis (ALS) research, the Department of Veterans Affairs Biorepository Brain Bank. Enrolled veterans receive biannual telephone follow-up to collect clinical data until death including the ALS Functional Rating Scale-Revised (ALSFRS-R). A comprehensive post mortem examination is performed and a wide range of fixed and frozen brain and spinal cord samples are banked. As of December 2012, 240 veterans were enrolled from 47 states and post mortem tissue recoveries were performed on 100 veterans from 37 states. Average disease duration was 13.5 (range 3−45) years. Average follow-up for living subjects was 3.1 years and average ALSFRS-R score was 23.5 compared to 25.9 (12−24 months earlier), indicating slow disease progression. ALS was confirmed by post mortem examination in 97% of cases. Eighty-six percent of cases were TDP-43-positive. Additional neuropathological diagnoses include Lewy body disease (13%), frontotemporal lobar degeneration (6.3%), chronic traumatic encephalopathy with motor neuron disease (3.2%), and Alzheimer's disease (2.1%). Tissue RIN values were ≥ 4.0 in 88% of cases. In conclusion, the availability of high quality fixed and frozen CNS tissue from this well characterized cohort is an important resource to facilitate research into genetic and environmental risk factors and clinical pathological relationships in ALS.

Key words::

• Neuropathology
• brain banking
• amyotrophic lateral sclerosis
• tissue banking
• survival
• prognostic

Acknowledgements

We thank those who assisted with the telephone assessments, tissue recovery coordination, data scoring, entry and accuracy checks at the Boston site: Shelley Amberg, Owen Harris and Therasia Roland. We also thank those who assisted in the processing and storage of the tissue samples at the following sites: Tucson, Sean Walker; Boston/Bedford, Kerry Cormier. Additionally, we thank Marianna Bledsoe and Kristina Hill at VAORD for their assistance in the administration and funding of the VABBB, and coordination of the tissue access committee. We thank Jean Paul Vonsattel and the New York Brain Bank at Columbia University, and Anil Prasad and Louis Fiore for their support in the initiation of the VABBB.

Finally, we are grateful to all the veterans who have decided to make this generous after-death organ donation supporting the VA's commitment to ALS research. We are also grateful to veterans’ families and caretakers who have done everything in their power to fulfill the veterans’ wishes of organ donation.

Declaration of interest: The authors report no conflicts of interest. The views expressed in this paper are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs.

The present work was supported by funds from the Cooperative Studies and Biomedical Laboratory Research and Development Programs of the United States Department of Veterans Affairs Office of Research and Development (VAORD). VAORD approved the manuscript for submission but was not involved in the design of the study or the collection, management, analysis, or interpretation of the data.

Some of the data presented in this manuscript was obtained via a Data Use Agreement between the VABBB and CSP Study #500A, National Registry of Veterans with Amyotrophic Lateral Sclerosis.