RT Journal Article
SR Electronic
T1 Lewy pathology in Parkinson’s disease consists of a crowded organellar membranous medley
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 137976
DO 10.1101/137976
A1 Sarah H. Shahmoradian
A1 Christel Genoud
A1 Alexandra Graff-Meyer
A1 Jürgen Hench
A1 Tim Moors
A1 Gabriel Schweighauser
A1 Jing Wang
A1 Kenneth N. Goldie
A1 Rosmarie Sütterlin
A1 Daniel Castaño-Díez
A1 Paula Pérez-Navarro
A1 Evelien Huisman
A1 Sabine Ipsen
A1 Angela Ingrassia
A1 Yvonne de Gier
A1 Annemieke J.M. Rozemuller
A1 Anne De Paepe
A1 Johannes Erny
A1 Andreas Staempfli
A1 Joerg Hoernschemeyer
A1 Frederik Großerüschkamp
A1 Daniel Niedieker
A1 Samir F. El-Mashtoly
A1 Marialuisa Quadri
A1 Wilfred F.J. van IJcken
A1 Vincenzo Bonifati
A1 Klaus Gerwert
A1 Bernd Bohrmann
A1 Stephan Frank
A1 Markus Britschgi
A1 Henning Stahlberg
A1 Wilma D. J. van de Berg
A1 Matthias E. Lauer
YR 2017
UL http://biorxiv.org/content/early/2017/05/16/137976.abstract
AB 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 α-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.