I am particularly grateful to my graduate students for all that they have taught me. I am also grateful to Professor James Ironside for his generous support and his encouragement. The monoclonal antibody MAR-1 used in CDI was generously supplied by Dr Albrecht Groener (CSL Behring, Marburg, Germany). The transgenic animal brains used in PMCA experiments were generously provided by Dr Rona Barron and Professor Jean Manson (Roslin Institute, The University of Edinburgh, UK). The
analysis of animal prion diseases was carried out in collaboration with Drs Martin C646 Jeffrey and Lorenzo Gonzalez (AHVLA, Lasswade, UK). Animal prion disease specimens were obtained by request from the AHVLA Biological Archive Group (Weybridge, UK). All human brain specimens were obtained by request from the Medical Research Council NCJDRSU Brain and Tissue Bank. Ethical approval for their use is covered by LREC 2000/4/157 (Prof J. W. Ironside). The development of PMCA was funded by the Chief Scientists Office of the Scottish Government (Grant reference CZB/4/357 and CZB/4/688) and through collaboration with the Scottish National Blood Transfusion
Service (Prof Marc Paclitaxel in vivo Turner, Dr Ian MacGregor and Dr Christopher Prowse) and UK Forum funding. The investigation of human stem cell responses to human prion infectivity was also supported by a Chief Scientists Office grant to Dr Paul De Sousa and colleagues (MRC Centre for Regenerative Medicine, University of Edinburgh) (Grant reference CZB/4/588). The work of the NCJDRSU is funded by the Department of Health, UK and by the Scottish Government. This is an independent report commissioned and funded by the Policy Research Program in the Department of Health, UK. The views expressed in the publication are those of the author and not necessarily those of the Department of Health. “
“FIG4 is a phosphatase that regulates intracellular vesicle trafficking along the endosomal-lysosomal pathway. Mutations of FIG4 lead to the development of Charcot-Marie-Tooth
disease type 4J and amyotrophic lateral sclerosis (ALS). Moreover, ALS-associated proteins (transactivation response DNA protein 43 (TDP-43), fused in sarcoma (FUS), optineurin, ubiquilin-2, charged mutivesicular body protein 2b (CHMP2B) and valosin-containing protein) BCKDHA are involved in inclusion body formation in several neurodegenerative diseases. Using immunohistochemistry, we examined the brains and spinal cords of patients with various neurodegenerative diseases, including sporadic TDP-43 proteinopathy (ALS and frontotemporal lobar degeneration). TDP-43 proteinopathy demonstrated no FIG4 immunoreactivity in neuronal inclusions. However, FIG4 immunoreactivity was present in Pick bodies in Pick’s disease, Lewy bodies in Parkinson’s disease and dementia with Lewy bodies, neuronal nuclear inclusions in polyglutamine and intranuclear inclusion body diseases, and Marinesco and Hirano bodies in aged control subjects.