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

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 

机构地区：[1]Amsterdam UMC,Department of Anatomy and Neurosciences,Section Clinical Neuroanatomy and Biobanking,Amsterdam Neuroscience,Vrije University Amsterdam,O|2 Life Sciences building,De Boelelaan 1108,1081 HZ Amster-dam,Netherlands [2]Amsterdam Neuroscience,Program Neurodegeneration,Amsterdam,the Netherlands [3]Amsterdam UMC,Department of Pathol-ogy,Amsterdam Neuroscience,Vrije University Amsterdam,De Boelelaan,Amsterdam,Netherlands [4]Department of Neurology,Erasmus Medical Center,Postbus 2040,3000 CA Rotterdam,Netherlands.

出　　处：《Translational Neurodegeneration》2022年第1期129-147,共19页转化神经变性病（英文）

基　　金：the Stichting ParkinsonFonds,SPF 38000,project number:105475.

摘　　要：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 circuitry.The insula,a cortical brain hub,was recently discovered to be highly vulnerable to pathology and plays a role in cognitive deficits in PD and DLB.The 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 DLB.Methods: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 stereology.Cytoskeletal damage was comprehensively studied using immunofluorescent multi-labelling and 3D confocal laser-scanning microscopy.Results: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 insula.Alternatively,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 dementia.Neurofilament and myelin showed degenerative changes including swellings,demyelination,and detachment of the axon-myelin unit.Conclusions: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 contributing to cognitive,emotional,and auton

关 键 词：Α-SYNUCLEIN Insular subregions Axonal length density Alzheimer’s disease pathology NEUROFILAMENT MYELIN 

分 类 号：R749.16[医药卫生—神经病学与精神病学]