Despite the huge advancements in understanding age-related neurodegenerative diseases, many of the fundamental questions related to what causes these diseases remain unanswered. One of the alterations that happens in affected brains is the deposition of abnormally folded proteins. The most common of these proteins is tau. The diseases that are characterized by the deposition of abnormal tau in the brain are known as the tau proteinopathies.
We have recently discovered a new tau proteinopathy in a very unlikely place. We found that an outbreak of a neurologic disease in northern Uganda, known as nodding syndrome, is associated with tau proteinopathy. This brain disease only affects children. The children first develop seizures and many then develop early-onset dementia and possibly Parkinsonism as young adults.
Nodding syndrome leads to severe neurological disability like the age-related neurodegenerative disorders. However, this outbreak of nodding syndrome only developed in a restricted cohort of African children in refugee camps during the time of internal armed conflict in Uganda. On this basis, we believe that there is an environmental factor, such as an infection or a toxin, which may have initiated the tau proteinopathy.
Our research is aimed at understanding how nodding syndrome can be used as a model to understand tau proteinopathies. Specifically, if we can determine the cause and pathogenesis of nodding syndrome in this unique and geographical isolated population, then we may be able to translate that knowledge into understanding how tau becomes abnormally folded and malfunctions in Alzheimer’s disease and related disorders.
The innovations and discoveries
Our group represents a North-south collaboration between Canada and Uganda. Our main contribution, to date, has been the systemic clinicopathological characterization of NS. Using classical methods and immunohistochemistry we described a novel pattern of tau deposition in the brains of fatal cases of nodding syndrome. We do not yet know how the tau proteinopathy in nodding syndrome syndrome is linked the the onset and progression of the disease. We have developed an interdisciplinary approach to answer this question using: pathology, biochemistry, genetics, epidemiology and intracerebral inoculation.
Michael Pollanen is a pathologist who has spent his entire career studying the pathology of vulnerable populations. These populations are rendered susceptible to morbidity and mortality on the basis of environmental factors, warfare, age, gender, and human rights abuses. He was instrumental in founding the discipline of forensic pathology in Canada. His extensive fieldwork in international forensic pathology resulted in the discovery of tau pathology in NS in Uganda. This discovery was facilitated by his PhD work in neurodegenerative disease many years ago, shortly after the Tanz CRND was opened.
BSc, University of Guelph
PhD, University of Toronto
MD, University of Toronto