Abstract 4
Category: Clinical Science
At the end of the session, participants will be able to:
- To appreciate the spectrum and frequency of co-pathologies.
- To identify common and rare neurodegenerative pathologies and their relation to clinical symptoms.
COI Disclosure:
None to disclose.
Shelley L. Forrest1,2, Nusrat Sadia3, Mozhgan Khodadadi3, Charles Tator3,4, Robin Green3,5, Maria Carmela Tartaglia3,6, Gabor G. Kovacs1,2,7,8
1Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, Ontario, Canada.
2Laboratory Medicine Program & Krembil Brain Institute, University Health Network, Toronto, Ontario, Canada.
3Canadian Concussion Centre, Krembil Brain Institute, University Health Network, and University of Toronto, Toronto, Ontario, Canada.
4Division of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada.
5KITE-Toronto Rehab, University Centre, Toronto, Ontario, Canada.
6University Health Network Memory Clinic & Krembil Brain Institute, University Health Network, Toronto, Ontario, Canada.
7Edmond J. Safra Program in Parkinson’s Disease, Rossy Program for PSP Research and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, Toronto, ON, Canada.
8Department of Laboratory Medicine and Pathobiology and Department of Medicine, University of Toronto, Toronto Ontario, Canada.
Presenter
I am a Senior Scientific Associate IV at the Tanz Centre for Research in Neurodegenerative Disease (CRND), University of Toronto. I completed my PhD in Neuroscience from The University of Sydney in 2013 and commenced postdoctoral training in the Discipline of Pathology, The University of Sydney. During this time, I acquired a deep knowledge of the cellular abnormalities characteristic of frontotemporal dementia (FTD) and related disorders, ageing and a range of neurodegenerative diseases. I have established national and international collaborations, and have been a member of international consortia that validated a novel age-related tauopathy. I am currently co-lead and coordinator of a large multicentre study, involving >25 research centres and brain banks from 9 countries, to correlate the anatomical distribution and severity of pathology in a recently described glial-predominant tauopathy. In 2020, I was recruited by the Dementia Research Centre as the Neuropathology Group Leader to facilitate the development of a neuropathology program of research combining human neurodegenerative
diseases and transgenic animal models of dementia and movement disorders. In 2022, I was recruited to the Tanz CRND to focus on human neurodegenerative diseases, in particular those with tau proteinopathies.
My research focuses on the neuropathology and disease mechanisms underlying FTD, ageing and a range of neurodegenerative disorders. In particular, my work involves the investigation of protein abnormalities
and cell types affected to determine the selective regional and cellular vulnerability in these disorders, and associated clinicopathological correlations.
Target Audience:
Pathologists, Residents, Medical Students
CanMEDS:
Communicator, Collaborator, Leader, Professional
Comparison of co-pathologies in CTE-NC and GGT and case report of an ex-football player
Abstract
Objective: To compare literature observations on the frequency and type of co-pathologies associated with chronic traumatic encephalopathy-neuropathological change (CTE-NC) and globular glial tauopathy (GGT). To report an ex-football player with primary progressive aphasia, and an unprecedented combination of degenerative pathologies, including CTE-NC.
Relevance: Mixed neurodegenerative pathologies are common, but can be overlooked when there is a more obvious pathology.
Methodology and case: 1) Literature review and summary of our observations in CTE and GGT cases. 2) A 86-year-old male former Canadian Football player was longitudinally followed in the Cognitive Neurology Clinic at Toronto Western Hospital and underwent clinical assessments and MRI scans throughout the disease course. Paraffin-embedded sections from all brain regions available were immunostained with histological and immunohistochemical stains.
Observations: Mixed pathologies are frequently associated with CTE-NC associated also with ageing. In GGT the frequency is lower but unusual co-pathology constellations (e.g. TDP-43) may occur. In the case presented, multiple and rare constellations of degenerative pathologies observed: 1) CTE-NC (high level); 2) High level of ADNC); 3) Lewy body disease (Braak stage 4 or limbic type); 4) Cerebral Amyloid Angiopathy; 5) Argyrophilic grain disease; 6) Globular Glial Tauopathy Type II (Corticospinal tract involvement) with selective and asymmetric involvement of the corticospinal tract; and 7) Neuronal intranuclear hyaline inclusion body disease.
Conclusions: This study highlights the spectrum of proteinopathies that can be associated with multiple concussions and demonstrates that unusual constellations of rare neurodegenerative diseases beyond ADNC and Lewy body pathology can be observed as co-pathologies in the same individuals.