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UID:20251111T072534EST-2126pXjW1h@132.216.98.100
DTSTAMP:20251111T122534Z
DESCRIPTION:To attend in person\, register here\n\nTo watch virtually\, cli
 ck here\n\n\nWilma D.J. van de Berg\n\nAssociate Professor\, Clinical Neur
 oanatomy and Biobanking\, Amsterdam UMC\, The Netherlands\n\nHost: Abbas S
 adikot\n\nAbstract: To design effective disease-modifying treatments for P
 arkinson’s disease (PD)\, a deeper understanding of the (sub)cellular dise
 ase mechanisms and selective vulnerability to proteinopathy is urgently ne
 eded. Alpha-synuclein (aSyn) pathology is the neuropathological hallmark o
 f PD and Dementia with Lewy bodies (DLB)\, but also frequently observed in
  AD and other neurodegenerative disorders at autopsy. Within Clinical Neur
 oanatomy\, we aim to define cellular disease mechanisms and translate this
  knowledge into pathology-specific MRI\, tissue and biofluid biomarkers fo
 r PD. We have developed a pipeline to study the aging and diseased postmor
 tem human brain at macro-to-nanoscale resolution1.\n\nWe recently showed t
 hat increased cortical neurofilament (NfL) levels and synaptic loss contri
 butes to cortical thinning in PD and correlates with increased cortical me
 an diffusivity in PD2. NfL-positive neurons showed degenerative morphologi
 cal features and axonal fragmentation. The increased NfL correlated with p
 Ser129-αSyn but more strongly with p-tau load in PDD. Using STED microscop
 y\, we discovered that pSer129 aSyn and truncated aSyn differ in subcellul
 ar localization and that pSer129 aSyn displays a cytoplasmic network in ea
 rly maturation stages of Lewy bodies in PD3. We demonstrated that aSyn agg
 regates in the soma and neurites of PD brains consists of accumulated memb
 ranes\, cellular vesicles and organelles in which fibrils could not always
  be detected4. In MSA brains\, we localized glial cytoplasmic inclusions (
 GCIs) and showed that they are composed of a meshwork of fuzzy filaments\,
  lysosomes\, autophagosomes. Using proteomic analysis\, we observed distin
 ct and overlapping molecular changes in between sporadic PD/DLB and GBA-ca
 rriers vs controls. Core mitochondrial proteins were more upregulated in t
 he substantia nigra of sporadic PD/DLB compared to GBA-PD/DLB and controls
 \, which was confirmed by mitochondrial morphological analysis by STED mic
 roscopy. Conversely\, lysosomal proteins were more severely downregulated 
 in GBA-PD/DLB versus sporadic including both GCase interacting proteins su
 ch as prosaposin and LIMP-2\, and other luminal enzymes such as cathepsin 
 B and cathepsin D ((unpublished data). Together\, our high-resolution mult
 icolor microscopy and molecular observations in the postmortem human brain
  provide novel insights into potential cellular disease mechanisms underly
 ing a regulated Lewy body morphogenesis and network dysregulation in PD.\n
 \nBio: Wilma D.J. van de Berg is Associate Professor\, group leader\, at t
 he dept. of Anatomy & Neurosciences of the Amsterdam UMC\, Vrije Universit
 y Amsterdam\, Director of the Normal Aging Brain Collection Amsterdam and 
 President of the Dutch Parkinson Scientists association\, Netherlands. She
  received her PhD in Cellular Neuroscience and at University of Maastricht
  in 2003. Afterwards\, she specialized in neuroanatomy and neuropathology 
 of Parkinson’s disease and related neurodegenerative disorders at VU Unive
 rsity Medical Center\, Amsterdam. Her research team Clinical Neuranatomy a
 nd Biobanking (CNAB) studies human brain morphology and protein aggregatio
 n in post-mortem human brain tissue of donors with Parkinson’s disease and
  related disorders from macro-to-nanoscale using advanced imaging methods.
  She co-leads the multicentre observational longitudinal cohort study ‘Pro
 filing Parkinson’s (ProPark)’ aiming to identify molecular profiles for st
 ratifying Parkinson patients for next clinical trials.\n\n\nSupported by t
 he generosity of the Killam Trusts\, the MNI's Killam Seminar Series invit
 es outstanding guest speakers whose research is of interest to the scienti
 fic community at the MNI and ɬÀï·¬.\n
DTSTART:20230606T200000Z
DTEND:20230606T210000Z
LOCATION:Jeanne Timmins Amphitheatre\, Montreal Neurological Institute\, CA
 \, QC\, Montreal\, H3A 2B4\, 3801 rue University
SUMMARY:Killam Seminar Series: Tales from the human brain: a multi-scale ap
 proach to elucidate pathogenic mechanisms involved in Parkinson’s
URL:/neuro/channels/event/killam-seminar-series-tales-
 human-brain-multi-scale-approach-elucidate-pathogenic-mechanisms-342357
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