Y Y Fathy1, A J Jonker1, E Oudejans1, F J J de Jong2, A-M W van Dam1, A J M Rozemuller3, W D J van de Berg1. 1. Section Clinical Neuroanatomy, Department of Anatomy and Neurosciences, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands. 2. Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands. 3. Department of Pathology, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.
Abstract
AIM: The insular cortex consists of a heterogenous cytoarchitecture and diverse connections and is thought to integrate autonomic, cognitive, emotional and interoceptive functions to guide behaviour. In Parkinson's disease (PD) and dementia with Lewy bodies (DLB), it reveals α-synuclein pathology in advanced stages. The aim of this study is to assess the insular cortex cellular and subregional vulnerability to α-synuclein pathology in well-characterized PD and DLB subjects. METHODS: We analysed postmortem insular tissue from 24 donors with incidental Lewy body disease, PD, PD with dementia (PDD), DLB and age-matched controls. The load and distribution of α-synuclein pathology and tyrosine hydroxylase (TH) cells were studied throughout the insular subregions. The selective involvement of von Economo neurons (VENs) in the anterior insula and astroglia was assessed in all groups. RESULTS: A decreasing gradient of α-synuclein pathology load from the anterior periallocortical agranular towards the intermediate dysgranular and posterior isocortical granular insular subregions was found. Few VENs revealed α-synuclein inclusions while astroglial synucleinopathy was a predominant feature in PDD and DLB. TH neurons were predominant in the agranular and dysgranular subregions but did not reveal α-synuclein inclusions or significant reduction in density in patient groups. CONCLUSIONS: Our study highlights the vulnerability of the anterior agranular insula to α-synuclein pathology in PD, PDD and DLB. Whereas VENs and astrocytes were affected in advanced disease stages, insular TH neurons were spared. Owing to the anterior insula's affective, cognitive and autonomic functions, its greater vulnerability to pathology indicates a potential contribution to nonmotor deficits in PD and DLB.
AIM: The insular cortex consists of a heterogenous cytoarchitecture and diverse connections and is thought to integrate autonomic, cognitive, emotional and interoceptive functions to guide behaviour. In Parkinson's disease (PD) and dementia with Lewy bodies (DLB), it reveals α-synuclein pathology in advanced stages. The aim of this study is to assess the insular cortex cellular and subregional vulnerability to α-synuclein pathology in well-characterized PD and DLB subjects. METHODS: We analysed postmortem insular tissue from 24 donors with incidental Lewy body disease, PD, PD with dementia (PDD), DLB and age-matched controls. The load and distribution of α-synuclein pathology and tyrosine hydroxylase (TH) cells were studied throughout the insular subregions. The selective involvement of von Economo neurons (VENs) in the anterior insula and astroglia was assessed in all groups. RESULTS: A decreasing gradient of α-synuclein pathology load from the anterior periallocortical agranular towards the intermediate dysgranular and posterior isocortical granular insular subregions was found. Few VENs revealed α-synuclein inclusions while astroglial synucleinopathy was a predominant feature in PDD and DLB. TH neurons were predominant in the agranular and dysgranular subregions but did not reveal α-synuclein inclusions or significant reduction in density in patient groups. CONCLUSIONS: Our study highlights the vulnerability of the anterior agranular insula to α-synuclein pathology in PD, PDD and DLB. Whereas VENs and astrocytes were affected in advanced disease stages, insular TH neurons were spared. Owing to the anterior insula's affective, cognitive and autonomic functions, its greater vulnerability to pathology indicates a potential contribution to nonmotor deficits in PD and DLB.
Authors: Kevin P Nguyen; Vyom Raval; Alex Treacher; Cooper Mellema; Fang Frank Yu; Marco C Pinho; Rathan M Subramaniam; Richard B Dewey; Albert A Montillo Journal: Parkinsonism Relat Disord Date: 2021-03-07 Impact factor: 4.891
Authors: Nathalie Philippi; Vincent Noblet; Malik Hamdaoui; David Soulier; Anne Botzung; Emmanuelle Ehrhard; Benjamin Cretin; Frédéric Blanc Journal: Alzheimers Res Ther Date: 2020-07-06 Impact factor: 6.982
Authors: Yasmine Y Fathy; Dagmar H Hepp; Frank J de Jong; Jeroen J G Geurts; Elisabeth M J Foncke; Henk W Berendse; Wilma D J van de Berg; Menno M Schoonheim Journal: Neuroimage Clin Date: 2020-07-25 Impact factor: 4.881