Abstract 13- 1045-1100
Category: Basic Science
At the end of the session,
participants will be able to:
- Describe the clinical and pathological features of nodding syndrome
- Discuss the involvement of Onchocerca volvulus in the cause and pathogenesis of nodding syndrome
- Contrast the signature cortical laminar distribution of nodding syndrome and primary tau proteinopathies
None to disclose.
My name is Kenneth Kodja, and I’m currently a graduate student pursuing an MSc in Laboratory Medicine and Pathobiology at the University of Toronto. Prior to graduate school, I completed an Honours Specialization in Neuroscience at the University of Toronto. My undergraduate program exposed me to various scientific fields and industries, but I was drawn to Laboratory Medicine and Pathobiology. My primary research interest regards investigating the cause and pathogenesis of Nodding syndrome.
Kenneth G. Kodja 1, 2, 3, Sylvester Onzivua 4, David Clutterbuck 2, David L. Kitara 5, Amanda Fong 2, Michael S. Pollanen 1, 2, 3
1 Department of Pathobiology and Laboratory Medicine, University of Toronto, Toronto, Ontario, Canada
2 Ontario Forensic Pathology Service, Toronto, Ontario, Canada
3 Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada
4 Department of Pathology, College of Health Sciences, Makerere University, Kampala, Uganda
5 Department of Surgery, Gulu University, Gulu, Uganda.
Pathologists, Residents, Medical Students
Nodding syndrome: characterizing the newest tau proteinopathy in Africa
Nodding syndrome (NS) is an acquired tau proteinopathy plaguing the remote rural communities in Eastern sub-Saharan Africa. It has been proposed that infection with the nematode parasite Onchocerca volvulus triggers an autoimmune attack against the human protein leiomodin-1. This theory is dependent on the constitutive neuronal expression of leiomodin-1. We tested this hypothesis by exploring the histologic distribution of this protein in the normal human brain. Subsequent immunostaining of cerebellar tissue and C. elegans (a proxy for Onchocerca volvulus) using an antibody recognizing the N-terminus of leiomodin-1 was conducted. Our study failed to identify the presence of leiomodin-1 immunoreactivity in neurons or glia. Our results also suggest the possibility of leiomodin-1 antibody cross-reactivity between human Purkinje cell membranes and the body wall of C. elegans; a finding explained by the homology between leiomodin-1 and tropomodulin. This outcome does not support the hypothesis of autoimmunity involving Onchocerca volvulus and leiomodin-1. We also investigate the signature laminar distribution of cortical tau pathology in NS. Through morphometric analysis, our current study, in agreement with the literature, suggests that primary tauopathies (the likes of progressive supranuclear palsy, corticobasal degeneration, Pick’s disease and globular glial tauopathy) are associated with severe lower layer (IV-VI) pathologic burden, independent of clinical symptomology. Interestingly, we found predominant involvement of the upper layers (I-III) in NS; a laminar profile similar to the amyotrophic lateral sclerosis and parkinsonism-dementia complex of Guam. The present study lays the foundation for future work investigating potentially unique mechanisms of propagation and neurodegeneration in NS.