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

Y. Y. Fathy, A. J. Jonker, E. Oudejans, F. J.J. de Jong, A. M.W. van Dam, A. J.M. Rozemuller, W. D.J. van de Berg

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)262-277
Number of pages16
JournalNeuropathology and Applied Neurobiology
Volume45
Issue number3
Early online date24 May 2018
DOIs
Publication statusPublished - 1 Apr 2019

Cite this

@article{ed94ec6959f24cf8ba1f6a9b03768340,
title = "Differential insular cortex subregional vulnerability to α-synuclein pathology in Parkinson's disease and dementia with Lewy bodies",
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.",
keywords = "alpha synuclein, astrocytes, insular cortex, Parkinson's disease, von Economo neurons, vulnerability",
author = "Fathy, {Y. Y.} and Jonker, {A. J.} and E. Oudejans and {de Jong}, {F. J.J.} and {van Dam}, {A. M.W.} and Rozemuller, {A. J.M.} and {van de Berg}, {W. D.J.}",
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language = "English",
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journal = "Neuropathology and Applied Neurobiology",
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Differential insular cortex subregional vulnerability to α-synuclein pathology in Parkinson's disease and dementia with Lewy bodies. / Fathy, Y. Y.; Jonker, A. J.; Oudejans, E.; de Jong, F. J.J.; van Dam, A. M.W.; Rozemuller, A. J.M.; van de Berg, W. D.J.

In: Neuropathology and Applied Neurobiology, Vol. 45, No. 3, 01.04.2019, p. 262-277.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Differential insular cortex subregional vulnerability to α-synuclein pathology in Parkinson's disease and dementia with Lewy bodies

AU - Fathy, Y. Y.

AU - Jonker, A. J.

AU - Oudejans, E.

AU - de Jong, F. J.J.

AU - van Dam, A. M.W.

AU - Rozemuller, A. J.M.

AU - van de Berg, W. D.J.

N1 - © 2018 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.

PY - 2019/4/1

Y1 - 2019/4/1

N2 - 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.

AB - 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.

KW - alpha synuclein

KW - astrocytes

KW - insular cortex

KW - Parkinson's disease

KW - von Economo neurons

KW - vulnerability

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U2 - 10.1111/nan.12501

DO - 10.1111/nan.12501

M3 - Article

VL - 45

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JO - Neuropathology and Applied Neurobiology

JF - Neuropathology and Applied Neurobiology

SN - 0305-1846

IS - 3

ER -