RT Journal Article
SR Electronic
T1 Insular cortex sub-region-dependent distribution pattern of α-synuclein immunoreactivity in Parkinson’s disease and dementia with Lewy bodies
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 156984
DO 10.1101/156984
A1 Yasmine Y. Fathy
A1 Frank Jan de Jong
A1 Anne-Marie van Dam
A1 Annemieke J.M. Rozemuller
A1 Wilma D.J. van de Berg
YR 2017
UL http://biorxiv.org/content/early/2017/06/28/156984.abstract
AB The insular cortex is a heterogeneous and widely connected brain region. It plays a role in autonomic, cognitive, emotional and somatosensory functions. Its complex and unique cytoarchitecture includes a periallocortical agranular, pro-isocortical dysgranular, and isocortical granular sub-regions. In Parkinson’s disease (PD), the insula shows α-synuclein inclusions in advanced stages of the disease and its atrophy correlates with cognitive deficits. However, little is known regarding its regional neuropathological characteristics and vulnerability in Lewy body diseases. The aim of this study is to assess the distribution pattern of α-synuclein pathology in the insular sub-regions and the selective vulnerability of its different cell types in PD and dementia with Lewy bodies (DLB). Human post-mortem insular tissues from 10 donors with incidental Lewy body disease (iLBD), PD, DLB, and age-matched controls were immunostained for α-synuclein and glial fibrillary acid protein (GFAP). Results showed that a decreasing gradient of α-synuclein pathology was present from agranular to granular sub-regions in iLBD, PD and PD with dementia (PDD) donors. The agranular insula was heavily inflicted, revealing various α-synuclein immunoreactive morphological structures, predominantly Lewy neurites (LNs), and astroglial synucleinopathy. While dysgranular and granular sub-regions showed a decreasing gradient of inclusions and more Lewy bodies (LBs) in deeper layers. In DLB, this gradient was less pronounced and severe pathology was observed in the granular insula compared to PDD and regardless of disease stage. Protoplasmic astrocytes showed α-synuclein inclusions and severe degenerative changes increasing with disease severity. While few von Economo neurons (VENs) in the fronto-insular region revealed inclusions, particularly in PDD patients. Our study reports novel findings on the differential involvement of the insular sub-regions in PD and particular involvement of the agranular sub-region, VENs and astrocytes. Thus, the differential cellular architecture of the insular sub-regions portrays the topographic variation and vulnerability to α-synuclein pathology in Lewy body diseases.AbbreviationsADAlzheimer’s diseaseARTAGAge related tauopathy of the astrogliaDLBDementia with Lewy bodiesGFAPgial fibrillary acidic proteiniLBDincidental Lewy body diseaseLBLewy bodiesLNLewy neuritesMOCMander’s overlap coefficientNFTNeurofibrillary tanglesPARTprimary age related tauopathyPCCPearson’s correlation coefficientPDParkinson’s diseasePDDParkinson’s disease with dementiaRBDREM sleep behavioral disorderVENsvon Economo neuronsVPAvaricose projection astrocytes