Activities per year
Abstract
Parkinson's disease, the most common age-related movement disorder, is a progressive neurodegenerative disease with unclear etiology. Key neuropathological hallmarks are Lewy bodies and Lewy neurites, which are neuronal inclusions that are immunopositive for the protein alpha-synuclein. In-depth ultrastructural analysis of Lewy pathology is key to understanding pathogenesis and progression of the disease. Using correlative light and electron microscopy on postmortem brain tissue of Parkinson's patients, we discovered a crowded membranous medley of vesicular structures, dysmorphic mitochondria and disrupted cytoskeletal elements in Lewy bodies and Lewy neurites, rather than the widely expected proteinacious filaments. The collapse and crowding of central organellar components was confirmed by stimulated emission-depletion microscopy, and chemical and optical imaging. A high lipid content was confirmed by lipidomics. The findings indicate ill-defined subcellular protein-lipid compartmentalization and point toward impaired organellar trafficking as a key driver of pathogenesis in Parkinson's disease.
Original language | English |
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Article number | doi: https://doi.org/10.1101/137976 |
Journal | Biorxiv |
Publication status | Published - 28 Jun 2017 |
Activities
- 1 Invited talk
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Tales of the human brain: multiscale imaging of Lewy body disease
Wilma van de Berg (Speaker)
17 Jun 2022Activity: Lecture / Presentation › Invited talk › Academic