Differential insular cortex subregional vulnerability to α-synuclein pathology in Parkinson's disease and dementia with Lewy bodies.

Y Y Fathy,A J M Rozemuller,A J Jonker,E Oudejans,W D J Van De Berg,F J J De Jong,A.‐M W Van Dam

doi:10.1111/nan.12501

Y Y Fathy, A J M Rozemuller + Show 5 more

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https://doi.org/10.1111/nan.12501

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Abstract

AimThe 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.MethodsWe 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.ResultsA 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.ConclusionsOur 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.

Highlights

We observed a decreasing gradient in the load of a-synuclein immunoreactivity from the anterior periallocortical agranular subregion to the intermediate pro-isocortical dysgranular and posterior isocortical granular insula in incidental Lewy body disease (iLBD), Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) subjects. This was evident in iLBD and PD(D) with the highest load of neuropathological inclusions in the agranular insula
Astrocytes were vulnerable to a-synuclein inclusions and showed degenerative changes at all disease stages, yet most prominent in PD with dementia (PDD) and DLB
The agranular insula comprises the highest density of acetylcholinesterase and lowest density of myelinated fibres while the opposite exists in the granular subregions [46]

Summary

Introduction

In PD and DLB, the catecholaminergic, dopaminergic and nor-adrenergic nuclei in the brainstem and cortex are vulnerable to a-synuclein pathology and degeneration [10] Loss of these monoaminergic neurons most likely contribute to the cognitive and neuropsychiatric deficits in these disorders [10,11]. Of interest in this respect, the insular cortex is involved in the integration of somatosensory and autonomic information with higher cognitive functions [12,13,14]. It plays a role in emotion recognition, cognition and awareness of interoceptive information and acts as the basis of selfawareness [15].

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