Frigerio, Irene;
Laansma, Max A;
Lin, Chen-Pei;
Hermans, Emma JM;
Bouwman, Maud MA;
Bol, John GJM;
Galis-de Graaf, Yvon;
... Jonkman, Laura E; + view all
(2023)
Neurofilament light chain is increased in the parahippocampal cortex and associates with pathological hallmarks in Parkinson’s disease dementia.
Translational Neurodegeneration
, 12
, Article 3. 10.1186/s40035-022-00328-8.
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Neurofilament light chain is increased in the parahippocampal cortex and associates with pathological hallmarks in Parkinson.pdf - Published Version Download (4MB) | Preview |
Abstract
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-β load) 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, neurofilament 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.
| Type: | Article |
|---|---|
| Title: | Neurofilament light chain is increased in the parahippocampal cortex and associates with pathological hallmarks in Parkinson’s disease dementia |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1186/s40035-022-00328-8 |
| Publisher version: | https://doi.org/10.1186/s40035-022-00328-8 |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
| Keywords: | Axonal degeneration, Cortical atrophy, Cortical thickness, Dementia with Lewy bodies, Mean diffusivity, Neurofilament, NfL, Parkinson’s disease, Parkinson’s disease dementia, Humans, Parkinson Disease, Dementia, Lewy Body Disease, Intermediate Filaments, Alzheimer Disease, Cerebral Cortex |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Brain Repair and Rehabilitation |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10164368 |
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