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Axonal degeneration in the anterior insular cortex is associated with Alzheimer’s co-pathology in Parkinson’s disease and dementia with Lewy bodies

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Translational Neurodegeneration 2022年第1期11卷 129-147页

作者： yasmine y.fathy Laura E.Jonkman John J.Bol Evelien Timmermans Allert J.Jonker Annemieke J.M.Rozemuller Wilma D.J.van de Berg Amsterdam UMC Department of Anatomy and NeurosciencesSection Clinical Neuroanatomy and BiobankingAmsterdam NeuroscienceVrije University AmsterdamO|2 Life Sciences buildingDe Boelelaan 11081081 HZ Amster-damNetherlands Amsterdam Neuroscience Program NeurodegenerationAmsterdamthe Netherlands Amsterdam UMC Department of Pathol-ogyAmsterdam NeuroscienceVrije University AmsterdamDe BoelelaanAmsterdamNetherlands Department of Neurology Erasmus Medical CenterPostbus 20403000 CA RotterdamNetherlands.

Background:Axons,crucial for impulse transmission and cellular trafficking,are thought to be primary targets of neurodegeneration in Parkinson’s disease(PD)and dementia with Lewy bodies(DLB).Axonal degeneration occurs early,preceeding and exceeding neuronal loss,and contributes to the spread of pathology,yet is poorly described outside the nigrostriatal *** insula,a cortical brain hub,was recently discovered to be highly vulnerable to pathology and plays a role in cognitive deficits in PD and *** aim of this study was to evaluate morphological features as well as burden of proteinopathy and axonal degeneration in the anterior insular sub-regions in PD,PD with dementia(PDD),and ***:α-Synuclein,phosphorylated(p-)tau,and amyloid-βpathology load were evaluated in the anterior insular(agranular and dysgranular)subregions of post-mortem human brains(n=27).Axonal loss was evaluated using modified Bielschowsky silver staining and quantified using *** damage was comprehensively studied using immunofluorescent multi-labelling and 3D confocal laser-scanning ***:Compared to PD and PDD,DLB showed significantly higherα-synuclein and p-tau pathology load,argyrophilic grains,and more severe axonal loss,particularly in the anterior agranular ***,the dysgranular insula showed a significantly higher load of amyloid-βpathology and its axonal density correlated with cognitive performance.p-Tau contributed most to axonal loss in the DLB group,was highest in the anterior agranular insula and significantly correlated with CDR global scores for *** and myelin showed degenerative changes including swellings,demyelination,and detachment of the axon-myelin ***:Our results highlight the selective vulnerability of the anterior insular sub-regions to various converging pathologies,leading to impaired axonal integrity in PD,PDD and DLB,disrupting their functional properties and potentially con

关键词： α-Synuclein Insular subregions Axonal length density Alzheimer’s disease pathology Neurofilament Myelin

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