Abstract 2
Category: Basic Science
At the end of the session, participants will be able to:
- To provide an overview of the atypical form of multiple system atrophy
- To demonstrate a new structure of -synuclein fold that is associated with peculiar limbic neuronal
inclusions - To discuss hippocampus involvement in MSA
COI Disclosure:
I have a relationship with a for-profit and/or a not-for-profit organization to disclose.
Name of for-profit or not-for-profit organization(s) : Mitsubishi-Tanabe, Ferrer companies
Description of relationship(s) : Single consultation
Name of for-profit or not-for-profit organization(s) : 5G4 synuclein antibody
Description of relationship(s) : Patent
Presenter
Gabor G. Kovacs MD PhD is Professor of Neuropathology and Neurology at the University of Toronto. He is Consultant Neuropathologist and Neurologist at the University Health Network (UHN) and a Principal Investigator at the
Tanz Centre for Research in Neurodegenerative Disease. Dr. Kovacs is the Co-Director of the Rossy Program for Progressive Supranuclear Palsy Research.
Dr. Kovacs completed his medical training at the Semmelweis University (Budapest, Hungary) where he specialized in Neurology and Neuropathology and obtained a PhD in Neuroscience. He was the leader of the Hungarian and Austrian Surveillance for Human Prion Diseases.
His major research has focused on the 1) Evaluation of the molecular pathological patterns associated with different genotypes and clinical syndromes of neurodegenerative diseases; 2) Definition of body-fluid biomarkers associated with morphologically defined phenotypes; and 3) Evaluation of selective vulnerability and pathogenesis-related proteins in the brain.
He has published more than 400 peer-reviewed papers and edited three books on Neuropathology.
ORCID: http://orcid.org/0000-0003-3841-5511
Gabor G. Kovacs1,2,3,4,5,6 Ivan Martinez-Valbuena1, Shelley L. Forrest1, Xiaoxiao Xu6, Renato P. Munhoz5, Jun Li1, Ekaterina Rogaeva1, Anthony E. Lang5, Masahiro Enomoto7
1Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Canada
2Krembil Brain Institute, University Health Network, Toronto, M5T 0S8, Ontario, Canada
3Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada;
4Laboratory Medicine Program, University Health Network, Toronto, Canada
5Edmond J. Safra Program in Parkinson’s Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, M5T 2S8, Toronto, Ontario, Canada
6Department of Medical Biophysics, University of Toronto, Toronto, Canada
7Princess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G 1L7, Canada.
Target Audience:
Pathologists, Residents, Medical Students, Other – Write In (Required): basic researchers
CanMEDS:
Medical Expert (the integrating role), Scholar
The relevance of identifying limbic neuronal synuclein pathology in multiple system atrophy
Abstract
Background: Two neuropathologically defined disorders that show consistently a-synuclein pathology include Lewy body diseases (LBD) and multiple system atrophy (MSA). MSA is characterized by predominantly oligodendroglial cytoplasmic inclusions and distinct synuclein protofilament folds.
Objective: To compare literature observations on hippocampal neuronal synuclein pathology in MSA and to address the question whether brain regions showing unusual neuronal a-synuclein pathology are associated with distinct biochemical and structural profile of a-synuclein as a distinctive feature of atypical form of MSA.
Methodology: Literature overview of MSA with limbic neuronal synuclein pathology (atypical MSA). Report of a case and comparison with typical cases of MSA using α-Synuclein seed amplification assay (α-Syn SAA), immunoblotting, Proteinase K digestions, Conformational stability assay (CSA) and Electron cryo-microscopy.
Observations: Neuronal cytoplasmic inclusions are thought to contribute to memory impairment when seen in the hippocampus in MSA and additionally large argyrophilic neuronal inclusions are detected in atypical MSA. In our case with atypical MSA, we demonstrate distinct biochemical characteristics of a-synuclein linked to cytopathological differences (e.g. neuronal or oligodendroglial) and a new Lewy-MSA hybrid fold brain regions showing neuronal inclusions.
Conclusions: We propose that cell-specific protein pathologies can be associated with distinct filament folds and expand the current structure-based classification of a-synucleinopathies.