Neurofilament light chain is increased in the parahippocampal cortex and associates with pathological hallmarks in Parkinson’s disease dementia  

作　　者：Irene Frigerio Max A.Laansma Chen-Pei Lin Emma J.M.Hermans Maud M.A.Bouwman John G.J.M.Bol Yvon Galis-de Graaf Dagmar H.Hepp Annemieke J.M.Rozemuller Frederik Barkhof Wilma D.J.van de Berg Laura E.Jonkman 

机构地区：[1]Section Clinical Neuroanatomy and Biobanking,Department of Anatomy and Neurosciences,Amsterdam UMC Location Vrije Universiteit Amsterdam,De Boelelaan 1118,Amsterdam,The Netherlands [2]Amsterdam Neuroscience,Neurodegeneration,Amsterdam,The Netherlands [3]Amsterdam Neurosci-ence,Brain Imaging,Amsterdam,The Netherlands [4]Department of Neurology,Amsterdam UMC Location Vrije Universiteit Amsterdam,De Boelelaan 1117,Amsterdam,The Netherlands [5]Department of Pathology,Amsterdam UMC Location Vrije Universiteit Amsterdam,De Boelelaan 1117,Amsterdam,The Netherlands [6]Department of Radiology and Nuclear Medicine,Amsterdam UMC Location Vrije Universiteit Amsterdam,De Boelelaan 1117,Amsterdam,The Netherlands [7]Institutes of Neurology and Healthcare Engineering,University College London,London,UK.

出　　处：《Translational Neurodegeneration》2023年第1期872-888,共17页转化神经变性病（英文）

基　　金：funded by The Michael J.Fox Foundation(grant#17253);Stichting ParkinsonFonds(grant#1881);supported by the NIHR biomedical research centre at the University College Hospital of London(UCLH).

摘　　要：Background Increased neurofilament levels in biofluids are commonly used as a proxy for neurodegeneration in several neurodegenerative disorders.In this study,we aimed to investigate the distribution of neurofilaments in the cerebral cortex of Parkinson’s disease(PD),PD with dementia(PDD)and dementia with Lewy bodies(DLB)donors,and its association with pathology load and MRI measures of atrophy and diffusivity.Methods Using a within-subject post-mortem MRI-pathology approach,we included 9 PD,12 PDD/DLB and 18 age-matched control donors.Cortical thickness and mean diffusivity(MD)metrics were extracted respectively from 3DT1 and DTI at 3T in-situ MRI.After autopsy,pathological hallmarks(pSer129-αSyn,p-tau and amyloid-βload)together with neurofilament light-chain(NfL)and phosphorylated-neurofilament medium-and heavy-chain(p-NfM/H)immunoreactivity were quantified in seven cortical regions,and studied in detail with confocal-laser scanning microscopy.The correlations between MRI and pathological measures were studied using linear mixed models.Results Compared to controls,p-NfM/H immunoreactivity was increased in all cortical regions in PD and PDD/DLB,whereas NfL immunoreactivity was increased in the parahippocampal and entorhinal cortex in PDD/DLB.NfL-positive neurons showed degenerative morphological features and axonal fragmentation.The increased p-NfM/H correlated with p-tau load,and NfL correlated with pSer129-αSyn but more strongly with p-tau load in PDD/DLB.Lastly,neuro-filament immunoreactivity correlated with cortical thinning in PD and with increased cortical MD in PDD/DLB.Conclusions Taken together,increased neurofilament immunoreactivity suggests underlying axonal injury and neurofilament accumulation in morphologically altered neurons with increased pathological burden.Importantly,we demonstrate that such neurofilament markers at least partly explain MRI measures that are associated with the neurodegenerative process.

关 键 词：NEUROFILAMENT NFL Axonal degeneration Parkinson’s disease Parkinson’s disease dementia Dementia with Lewy bodies Cortical thickness Cortical atrophy Mean diffusivity 

分 类 号：R742.5[医药卫生—神经病学与精神病学]