Absence of heparan sulfate proteoglycans in Lewy bodies and Lewy neurites in Parkinson's disease brains.
alpha-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 alpha-synuclein deposition and fibrillization in these alpha-synucleinopathies. In order to better understand the pathogenesis of alpha-synucleinopathies it is important to identify molecules that regulate the fibrillization of alpha-synuclein. Since it has been demonstrated that heparan sulfate proteoglycans (HSPGs) and glycosaminoglycans (GAGs) promote the conversion of non-fibrillar amyloid beta-protein (Abeta) into neurotoxic fibrillar Abeta in Alzheimer's disease, they might also be involved in alpha-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 alpha-synuclein fibrillization and stabilization occurs independently of the presence of HSPGs or GAGs.
van Horssen
Jack
J
Department of Pathology, University Medical Center, Nijmegen, The Netherlands.
de Vos
Rob A I
RA
Steur
Ernst N H Jansen
EN
David
Guido
G
Wesseling
Pieter
P
de Waal
Robert M W
RM
Verbeek
Marcel M
MM
D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology; D001921:Brain / Q000276:immunology / Q000378:metabolism; D002449:Cell Aggregation / Q000502:physiology; D005260:Female; D006025:Glycosaminoglycans / Q000276:immunology / Q000378:metabolism; D006179:Gyrus Cinguli / Q000276:immunology / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D016631:Lewy Bodies / Q000276:immunology / Q000378:metabolism*; D008297:Male; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism; D016501:Neurites / Q000276:immunology / Q000378:metabolism*; D016874:Neurofibrillary Tangles / Q000276:immunology / Q000378:metabolism; D010300:Parkinson Disease / Q000276:immunology / Q000378:metabolism*; D051843:Synucleins; D051844:alpha-Synuclein
D000911:Antibodies, Monoclonal; D006025:Glycosaminoglycans; D019812:Heparan Sulfate Proteoglycans; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein