Affiliations: [a] Department of Pathology, University Medical Center, Nijmegen, The Netherlands | [b] Laboratorium Pathologie Oost Nederland, Enschede, The Netherlands | [c] Department of Neurology, Medisch Spectrum Twente, Enschede, The Netherlands | [d] The Center for Human Genetics, University of Leuven and Flanders Interuniversity Institute for Biotechnology, Leuven, Belgium | [e] Department of Neurology, University Medical Center, Nijmegen, The Netherlands
Correspondence:
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Corresponding author: Marcel M. Verbeek, Department of Neurology, University Medical Center Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Tel.: +31 2436 15192; Fax: +31 2435 40297; E-mail: [email protected].
Abstract: α-Synuclein is the major constituent of Lewy bodies and Lewy neurites in Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Relatively little is known about the exact mechanism of α-synuclein deposition and fibrillization in theseα-synucleinopathies. In order to better understand the pathogenesis of α-synucleinopathies it is important to identify molecules that regulate the fibrillization of α-synuclein. Since it has been demonstrated that heparan sulfate proteoglycans (HSPGs) and glycosaminoglycans (GAGs) promote the conversion of non-fibrillar amyloid β-protein (Aβ) into neurotoxic fibrillar Aβ in Alzheimer's disease, they might also be involved in α-synuclein aggregation. It was the aim of our study to examine the distribution pattern of these macromolecules in PD brains and the possible association with Lewy bodies and Lewy neurites. Although HSPGs clearly colocalized with senile plaques, we were unable to identify HSPGs or GAGs in Lewy bodies and Lewy neurites and therefore concluded that it is likely that α-synuclein fibrillization and stabilization occurs independently of the presence of HSPGs or GAGs.
