Evidence map›Paper›PMID 36658627›Full record

ArticleTranslational neurodegeneration2023

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

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 and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Translational neurodegeneration, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 2 pooled it
7.8field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 38 citations in OpenAlex.

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  16. Changes in Action Tremor in Parkinson's Disease over Time: Clinical and Neuroimaging Correlates.Movement disorders : official journal of the Movement Disorder Society · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 2 countries.

Irene FrigerioSection Clinical Neuroanatomy and Biobanking, Department of Anatomy and Neurosciences, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1118, Amsterdam, The Netherlands. i.frigerio@amsterdamumc.nl.ORCID 0000-0003-1780-2862
Max A LaansmaSection Clinical Neuroanatomy and Biobanking, Department of Anatomy and Neurosciences, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1118, Amsterdam, The Netherlands.
Chen-Pei LinSection Clinical Neuroanatomy and Biobanking, Department of Anatomy and Neurosciences, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1118, Amsterdam, The Netherlands.
Emma J M HermansSection Clinical Neuroanatomy and Biobanking, Department of Anatomy and Neurosciences, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1118, Amsterdam, The Netherlands.
Maud M A BouwmanSection Clinical Neuroanatomy and Biobanking, Department of Anatomy and Neurosciences, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1118, Amsterdam, The Netherlands.
John G J M BolSection Clinical Neuroanatomy and Biobanking, Department of Anatomy and Neurosciences, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1118, Amsterdam, The Netherlands.
Yvon Galis-de GraafSection Clinical Neuroanatomy and Biobanking, Department of Anatomy and Neurosciences, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1118, Amsterdam, The Netherlands.
Dagmar H HeppSection Clinical Neuroanatomy and Biobanking, Department of Anatomy and Neurosciences, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1118, Amsterdam, The Netherlands.
Annemieke J M RozemullerDepartment of Pathology, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands.
Frederik BarkhofAmsterdam Neuroscience, Brain Imaging, Amsterdam, The Netherlands.
Wilma D J van de BergSection Clinical Neuroanatomy and Biobanking, Department of Anatomy and Neurosciences, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1118, Amsterdam, The Netherlands.
Laura E JonkmanSection Clinical Neuroanatomy and Biobanking, Department of Anatomy and Neurosciences, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1118, Amsterdam, The Netherlands.
Amsterdam Neuroscience · NLAmsterdam University Medical Centers · NLNetherlands Institute for Neuroscience · NL

Funding

Department of Health
6 · The paper itself

Abstract

backgroundIncreased 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.

methodsUsing 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.

resultsCompared 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.

conclusionsTaken 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.

Indexed as

Alzheimer DiseaseDementiaLewy Body DiseaseParkinson DiseaseCerebral CortexHumansIntermediate FilamentsAxonal degenerationCortical atrophyCortical thicknessDementia with Lewy bodiesMean diffusivityNeurofilamentNfLParkinson’s diseaseParkinson’s disease dementia

Identifiers

PMID36658627
PMCPMC9854202
OpenAlexW4317513169

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.