Abstract
BackgroundThe role of both microglial activation and alpha-synuclein deposition in Parkinson's disease remain unclear. We have tested the hypothesis that if microglia play a primary role in Parkinson's disease pathogenesis, the microglial "activated" phenotype should be associated with histopathological and/or clinical features of the disease.MethodsWe have examined microglial MHC class II expression, a widely used marker of microglial activation, the occurrence of CD68-positive phagocytes and alpha-synuclein immunoreactivity in post-mortem human substantia nigra affected by idiopathic Parkinson's disease (PD). Using semi-quantitative severity ratings, we have examined the relationship between microglial activation, alpha-synuclein deposition, classical neuropathological criteria for PD, subtype of the disease and clinical course.ResultsWhile we did not observe an association between microglial MHC class II expression and clinical parameters, we did find a correlation between disease duration and the macrophage marker CD68 which is expressed by phagocytic microglia. In addition, we observed a significant correlation between the degree of MHC class II expression and alpha-synuclein deposition in the substantia nigra in PD.ConclusionWhile microglia appeared to respond to alpha-synuclein deposition, MHC class II antigen expression by microglia in the substantia nigra cannot be used as an indicator of clinical PD severity or disease progression. In addition, a contributory or even causative role for microglia in the neuronal loss associated with PD as suggested by some authors seems unlikely. Our data further suggest that an assessment of microglial activation in the aged brain on the basis of immunohistochemistry for MHC class II antigens alone should be done with caution.
Highlights
The role of both microglial activation and alpha-synuclein deposition in Parkinson's disease remain unclear
We independently evaluate the severity of alpha-synuclein deposition and microglial activation identified by immunohistochemical staining in the substantia nigra pars compacta (SN) in a large cohort of clinically and pathologically confirmed Parkinson's disease (PD) cases
We have studied the microglial response in PD on two levels, by observing MHC class II antigens (MHCII) -immunoreactive cells and CD68-immunopositive macrophages
Summary
We have examined microglial MHC class II expression, a widely used marker of microglial activation, the occurrence of CD68-positive phagocytes and alpha-synuclein immunoreactivity in post-mortem human substantia nigra affected by idiopathic Parkinson's disease (PD). Additional tissue sections from 17 other cases came from a previous study originally performed at the Institute of Neuropathology, University of Munich, Germany. These Parkinson's cases had been previously diagnosed, neuropathologically screened for confounding pathology, and examined in a study of apoptosis and microglial activation [15]. Neuropathological assessment was based on slides provided by the PDSTB for alpha-synuclein, tau and beta-amyloid immunohistochemistry of superior frontal gyrus, the hippocampal region and midbrain as minimum data sets, and screening of the cases for confounding pathology was based on hematoxylin and eosin examination of a standard series of 18 tissue blocks following a standardised dissection procedure [16]. Nine cases showed varying degrees of concurrent Alzheimer's disease (AD)-type pathology
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
