Neurofilament Levels Are Reflecting the Loss of Presynaptic Dopamine Receptors in Movement Disorders

Aims: Neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH) are biomarkers for neuroaxonal damage. We assessed whether NfL and other biomarker levels in the CSF are correlated to the loss of presynaptic dopamine transporters in neurons as detected with dopamine transpor...

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Autores principales:	Elena Diekämper, Britta Brix, Winfried Stöcker, Stefan Vielhaber, Imke Galazky, Michael C. Kreissl, Philipp Genseke, Emrah Düzel, Péter Körtvelyessy
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	neurofilament light chain movement disorders DaTscan Parkinson’s Disease CSF alpha-synuclein Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/c75d63963c094a3a86857a4e74a006a6
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spelling	oai:doaj.org-article:c75d63963c094a3a86857a4e74a006a62021-12-03T17:06:29ZNeurofilament Levels Are Reflecting the Loss of Presynaptic Dopamine Receptors in Movement Disorders1662-453X10.3389/fnins.2021.690013https://doaj.org/article/c75d63963c094a3a86857a4e74a006a62021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnins.2021.690013/fullhttps://doaj.org/toc/1662-453XAims: Neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH) are biomarkers for neuroaxonal damage. We assessed whether NfL and other biomarker levels in the CSF are correlated to the loss of presynaptic dopamine transporters in neurons as detected with dopamine transporter SPECT (DaTscan).Methods: We retrospectively identified 47 patients (17 Alzheimer’s dementia, 10 idiopathic Parkinson’s disease, 7 Lewy body dementia, 13 progressive supranuclear palsy or corticobasal degeneration) who received a DaTscan and a lumbar puncture. DaTscan imaging was performed according to current guidelines, and z-scores indicating the decrease in uptake were software based calculated for the nucleus caudatus and putamen. The CSF biomarkers progranulin, total-tau, alpha-synuclein, NfL, and pNfH were correlated with the z-scores.Results: DaTscan results in AD patients did not correlate with any biomarker. Subsuming every movement disorder with nigrostriatal neurodegeneration resulted in a strong correlation between putamen/nucleus caudatus and NfL (nucleus caudatus right p < 0.01, putamen right p < 0.05, left p < 0.05) and between pNfH and putamen (right p < 0.05; left p < 0.042). Subdividing in disease cohorts did not reveal significant correlations. Progranulin, alpha-synuclein, and total-tau did not correlate with DaTscan results.Conclusion: We show a strong correlation of NfL and pNfH with pathological changes in presynaptic dopamine transporter density in the putamen concomitant to nigrostriatal degeneration. This correlation might explain the reported correlation of impaired motor functions in PD and NfL as seen before, despite the pathological heterogeneity of these diseases.Elena DiekämperBritta BrixWinfried StöckerStefan VielhaberImke GalazkyMichael C. KreisslPhilipp GensekeEmrah DüzelEmrah DüzelPéter KörtvelyessyPéter KörtvelyessyPéter KörtvelyessyFrontiers Media S.A.articleneurofilament light chainmovement disordersDaTscanParkinson’s DiseaseCSFalpha-synucleinNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Neuroscience, Vol 15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	neurofilament light chain movement disorders DaTscan Parkinson’s Disease CSF alpha-synuclein Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	neurofilament light chain movement disorders DaTscan Parkinson’s Disease CSF alpha-synuclein Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Elena Diekämper Britta Brix Winfried Stöcker Stefan Vielhaber Imke Galazky Michael C. Kreissl Philipp Genseke Emrah Düzel Emrah Düzel Péter Körtvelyessy Péter Körtvelyessy Péter Körtvelyessy Neurofilament Levels Are Reflecting the Loss of Presynaptic Dopamine Receptors in Movement Disorders
description	Aims: Neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH) are biomarkers for neuroaxonal damage. We assessed whether NfL and other biomarker levels in the CSF are correlated to the loss of presynaptic dopamine transporters in neurons as detected with dopamine transporter SPECT (DaTscan).Methods: We retrospectively identified 47 patients (17 Alzheimer’s dementia, 10 idiopathic Parkinson’s disease, 7 Lewy body dementia, 13 progressive supranuclear palsy or corticobasal degeneration) who received a DaTscan and a lumbar puncture. DaTscan imaging was performed according to current guidelines, and z-scores indicating the decrease in uptake were software based calculated for the nucleus caudatus and putamen. The CSF biomarkers progranulin, total-tau, alpha-synuclein, NfL, and pNfH were correlated with the z-scores.Results: DaTscan results in AD patients did not correlate with any biomarker. Subsuming every movement disorder with nigrostriatal neurodegeneration resulted in a strong correlation between putamen/nucleus caudatus and NfL (nucleus caudatus right p < 0.01, putamen right p < 0.05, left p < 0.05) and between pNfH and putamen (right p < 0.05; left p < 0.042). Subdividing in disease cohorts did not reveal significant correlations. Progranulin, alpha-synuclein, and total-tau did not correlate with DaTscan results.Conclusion: We show a strong correlation of NfL and pNfH with pathological changes in presynaptic dopamine transporter density in the putamen concomitant to nigrostriatal degeneration. This correlation might explain the reported correlation of impaired motor functions in PD and NfL as seen before, despite the pathological heterogeneity of these diseases.
format	article
author	Elena Diekämper Britta Brix Winfried Stöcker Stefan Vielhaber Imke Galazky Michael C. Kreissl Philipp Genseke Emrah Düzel Emrah Düzel Péter Körtvelyessy Péter Körtvelyessy Péter Körtvelyessy
author_facet	Elena Diekämper Britta Brix Winfried Stöcker Stefan Vielhaber Imke Galazky Michael C. Kreissl Philipp Genseke Emrah Düzel Emrah Düzel Péter Körtvelyessy Péter Körtvelyessy Péter Körtvelyessy
author_sort	Elena Diekämper
title	Neurofilament Levels Are Reflecting the Loss of Presynaptic Dopamine Receptors in Movement Disorders
title_short	Neurofilament Levels Are Reflecting the Loss of Presynaptic Dopamine Receptors in Movement Disorders
title_full	Neurofilament Levels Are Reflecting the Loss of Presynaptic Dopamine Receptors in Movement Disorders
title_fullStr	Neurofilament Levels Are Reflecting the Loss of Presynaptic Dopamine Receptors in Movement Disorders
title_full_unstemmed	Neurofilament Levels Are Reflecting the Loss of Presynaptic Dopamine Receptors in Movement Disorders
title_sort	neurofilament levels are reflecting the loss of presynaptic dopamine receptors in movement disorders
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/c75d63963c094a3a86857a4e74a006a6
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Neurofilament Levels Are Reflecting the Loss of Presynaptic Dopamine Receptors in Movement Disorders

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