Abstract 7 – 1330-1345
Category: Basic Science

At the end of the session,
participants will be able to:

To understand the basis of abnormal iron accumulation in vulnerable regions of PSP diseased human brains.

To understand the patterns of pathological iron accumulation in PSP affected nuclei .

To demonstrate different patterns of cellular iron burden by iron species.



Dr. Seojin Lee – I am a PhD candidate at the University of Toronto, Faculty of Medicine, as part of Dr. Kovacs’ Lab at the TANZ Centre for Research in Neurodegenerative Diseases. My studies focus on the role of iron dysregulation in the early selective vulnerability patterns of Progressive Supranuclear Palsy (PSP) brains. My work extends to other proteinopathies associated with abnormal iron dysregulation.


Seojin Lee1, Ivan Martinez-Valbuena1, Suganthini Ilaalagan1,3, Naomi P. Visanji2,4, Gabor G. Kovacs1,2,3,4

1Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, Ontario, Canada;

2Department of Laboratory Medicine and Pathobiology and Department of Medicine, University of Toronto, Toronto, Ontario, Canada;

3Laboratory Medicine Program & Krembil Brain Institute, University Health Network, Toronto, Ontario, Canada;

4Edmund J Safra Program in Parkinson’s Disease and Rossy Program in Progressive Supranuclear Palsy, Toronto Western Hospital, 399 Bathurst St, Toronto, Ontario, M5T 2S8, Canada

Target Audience: 


Linking Iron homeostasis to vulnerability patterns in progressive supranuclear palsy


Progressive Supranuclear Palsy (PSP) is a 4-repeat tauopathy which pathology starts in select subcortical areas including the globus pallidus (GP) and the substantia nigra (SN), regions also associated with age-related iron accumulation. Toxic iron burden in these regions of PSP brains have been examined but given the differences in cellular iron homeostasis across cell types and the heterogeneity in PSP tau cytopathology, we aim to examine the possible role of iron accumulation on the cellular selective vulnerability of tau pathology in the vulnerable anatomical regions of PSP brains. Using human post-mortem brain tissue of the early-affected PSP brain regions (GP, SN, and putamen), we visualized iron deposition in the neurons, astroglia, oligodendrocytes, and microglia using a combination of DAB-enhanced Perl’s (ferric) and Turnbull (ferrous) iron staining with immunohistochemistry of cell type-specific markers. Iron deposition was also examined in relation to their tau cytopathologies using AT8-immunohistochemistry. In all three regions, astrocytes and microglia were seen to predominantly accumulate both species of iron. Moreover, tau-positive astrocytes showed the highest frequency of cellular iron deposition compared to neurofibrillary tangles and oligodendroglial coiled bodies. On the other hand, association of iron burden with different cellular tau pathologies was species-specific in the same regions, suggesting iron functions in PSP tau cytopathology may be distinct by species. Our mapping of cellular iron burden in relation to pathology in PSP brains suggests a selective cellular vulnerability to iron deposition in diseased brains, and further supports the role of pathological iron in the early pathogenesis of PSP.