Plasma NfL, GFAP, amyloid, and p-tau species as Prognostic biomarkers in Parkinson's disease

doi:10.1007/s00415-024-12669-7

. 2024 Dec;271(12):7537-7546.

doi: 10.1007/s00415-024-12669-7. Epub 2024 Sep 9.

Plasma NfL, GFAP, amyloid, and p-tau species as Prognostic biomarkers in Parkinson's disease

Andrea Pilotto^#^{1

2

3}, Nicholas J Ashton^#^{4

5

6

7}, Alessandro Lupini^#⁸, Beatrice Battaglio⁸, Cinzia Zatti⁸, Chiara Trasciatti^{8

9

10}, Stefano Gipponi⁸, Elisabetta Cottini⁹, Ilaria Grossi¹¹, Alessandro Salvi¹¹, Giuseppina de Petro¹¹, Marina Pizzi¹², Antonio Canale¹³, Kaj Blennow^{4

14

15

16

17}, Henrik Zetterberg^{4

14

18

19

20

21}, Alessandro Padovani^{8

9

10

22}

Affiliations

¹ Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, P.Zzale Spedali Civili, 1, 25123, Brescia, Italy. Andrea.pilotto@unibs.it.
² Department of Continuity of Care and Frailty, Neurology Unit, ASST Spedali Civili Hospital, Brescia, Italy. Andrea.pilotto@unibs.it.
³ Neurobiorepository and Laboratory of Advanced Biological Markers, University of Brescia and ASST Spedali Civili Hospital, Brescia, Italy. Andrea.pilotto@unibs.it.
⁴ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁵ Wallenberg Centre for Molecular and Translational Medicine, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
⁶ King's College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London, UK.
⁷ NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK.
⁸ Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, P.Zzale Spedali Civili, 1, 25123, Brescia, Italy.
⁹ Department of Continuity of Care and Frailty, Neurology Unit, ASST Spedali Civili Hospital, Brescia, Italy.
¹⁰ Neurobiorepository and Laboratory of Advanced Biological Markers, University of Brescia and ASST Spedali Civili Hospital, Brescia, Italy.
¹¹ Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
¹² Division of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
¹³ Department of Statistical Sciences, University of Padova, Padua, Italy.
¹⁴ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
¹⁵ Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France.
¹⁶ Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, Department of Neurology, Institute On Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of USTC, Hefei, People's Republic of China.
¹⁷ Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
¹⁸ UK Dementia Research Institute at UCL, London, UK.
¹⁹ Department of Old Age Psychiatry, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.
²⁰ Hong Kong Center for Neurodegenerative Diseases, Hong Kong, People's Republic of China.
²¹ Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
²² Brain Health Center, University of Brescia, Brescia, Italy.

^# Contributed equally.

PMID: 39249107
PMCID: PMC11588809
DOI: 10.1007/s00415-024-12669-7

Plasma NfL, GFAP, amyloid, and p-tau species as Prognostic biomarkers in Parkinson's disease

Andrea Pilotto et al. J Neurol. 2024 Dec.

. 2024 Dec;271(12):7537-7546.

doi: 10.1007/s00415-024-12669-7. Epub 2024 Sep 9.

Authors

Affiliations

¹ Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, P.Zzale Spedali Civili, 1, 25123, Brescia, Italy. Andrea.pilotto@unibs.it.
² Department of Continuity of Care and Frailty, Neurology Unit, ASST Spedali Civili Hospital, Brescia, Italy. Andrea.pilotto@unibs.it.
³ Neurobiorepository and Laboratory of Advanced Biological Markers, University of Brescia and ASST Spedali Civili Hospital, Brescia, Italy. Andrea.pilotto@unibs.it.
⁴ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁵ Wallenberg Centre for Molecular and Translational Medicine, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
⁶ King's College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London, UK.
⁷ NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK.
⁸ Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, P.Zzale Spedali Civili, 1, 25123, Brescia, Italy.
⁹ Department of Continuity of Care and Frailty, Neurology Unit, ASST Spedali Civili Hospital, Brescia, Italy.
¹⁰ Neurobiorepository and Laboratory of Advanced Biological Markers, University of Brescia and ASST Spedali Civili Hospital, Brescia, Italy.
¹¹ Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
¹² Division of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
¹³ Department of Statistical Sciences, University of Padova, Padua, Italy.
¹⁴ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
¹⁵ Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France.
¹⁶ Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, Department of Neurology, Institute On Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of USTC, Hefei, People's Republic of China.
¹⁷ Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
¹⁸ UK Dementia Research Institute at UCL, London, UK.
¹⁹ Department of Old Age Psychiatry, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.
²⁰ Hong Kong Center for Neurodegenerative Diseases, Hong Kong, People's Republic of China.
²¹ Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
²² Brain Health Center, University of Brescia, Brescia, Italy.

^# Contributed equally.

PMID: 39249107
PMCID: PMC11588809
DOI: 10.1007/s00415-024-12669-7

Abstract

Introduction: The prognostic role of plasma neurofilament light chain (NfL), phospho-tau, beta-amyloid, and GFAP is still debated in Parkinson's disease (PD).

Methods: Plasma p-tau181, p-tau231, Aβ1-40, Aβ1-42, GFAP, and NfL were measured by SIMOA in 136 PD with 2.9 + 1.7 years of follow-up and 76 controls. Differences in plasma levels between controls and PD and their correlation with clinical severity and progression rates were evaluated using linear regression analyses.

Results: Patients exhibited similar distribution of plasma biomarkers but higher P-tau181, P-tau231 and lower Aβ1-42 compared with controls. NfL and GFAP correlated with baseline motor and non-motor severity measures. At follow-up, NfL emerged as the best predictor of progression with marginal effect of GFAP and p-tau181 adjusting for age, sex, disease duration, and baseline motor severity.

Conclusion: The present findings confirmed plasma NfL as best predictor of progression in PD, with a marginal role of p-tau181 and GFAP.

Keywords: GFAP; Neurofilament light chain; Parkinson’s disease; Phosphorylated tau; Plasma biomarkers; Progression.

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Conflict of interest statement

Declarations. Conflicts of interest: All the authors report no disclosures related to this manuscript. Andrea Pilotto served in the advisory board of Z-cube (technology division of Zambon pharmaceuticals); he received honoraria from Z-cube s.r.l., Biomarin, Zambon, Nutricia and Chiesi Pharmaceuticals. He received research support from Vitaflo Germany and Zambon Italy. Nicholas Ashton has no financial conflicts to disclose. Alessandro Lupini has no financial conflicts to disclose. Beatrice Battaglio has no financial conflicts to disclose. Cinzia Zatti has no financial conflicts to disclose. Chiara Trasciatti has no financial conflicts to disclose. Stefano Gipponi has no financial conflicts to disclose. Elisabetta Cottini has no financial conflicts to disclose. Ilaria Grossi has no financial conflicts to disclose. Alessandro Salvi has no financial conflicts to disclose. Giuseppina De Petro has no financial conflicts to disclose. Marina Pizzi has no financial conflicts to disclose. Antonio Canale has no financial conflicts to disclose. Kaj Blennow has no financial conflicts to disclose. Henrik Zetterberg has served at scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Annexon, Apellis, Artery Therapeutics, AZTherapies, CogRx, Denali, Eisai, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, Biogen, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). Alessandro Padovani is consultant and served on the scientific advisory board of GE Healthcare, Eli-Lilly and Actelion Ltd Pharmaceuticals, received speaker honoraria from Nutricia, PIAM, Lansgstone Technology, GE Healthcare, Lilly, UCB Pharma, and Chiesi Pharmaceuticals. He is founded by Grant of M1.

Figures

**Fig. 1**
Correlation matrix including age at onset, disease duration, and the biomarkers analyzed in the cohort. p-tau181, phosphorylated Tau 181, p-tau231, phosphorylated Tau 231, Aβ1-40, beta-amyloid 1–40; Aβ1-42, beta-amyloid 1–42; *GFAP* Glial Fibrillary Acidic Protein, *NfL* neurofilament light chain; HC healthy controls; SP PD with slow motor progression; FP PD with fast motor progression

**Fig. 2**
Cox regression analysis comparing development of dementia in patients with high NFL levels vs patients with normal NFL levels. *NfL* neurofilament light chain

**Fig. 3**
Differences in biomarkers levels in plasma between HC, and slow and fast PD progressors. p-tau181, phosphorylated tau 181, p-tau231, phosphorylated tau 231, Aβ1-40, beta-amyloid 1–40; Aβ 1–42, beta-amyloid 1–42; *GFAP* glial fibrillary acidic protein, *NfL* neurofilament light chain

See this image and copyright information in PMC

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References

1. Espay AJ, Schwarzschild MA, Tanner CM, Fernandez HH, Simon DK, Leverenz JB et al (2017) Biomarker-driven phenotyping in Parkinson’s disease: a translational missing link in disease-modifying clinical trials. Mov Disord 32:319–324 - PMC - PubMed
1. Fereshtehnejad S-M, Romenets SR, Anang JBM, Latreille V, Gagnon J-F, Postuma RB (2015) New clinical subtypes of Parkinson disease and their longitudinal progression: a prospective cohort comparison with other phenotypes. JAMA Neurol 72:863–873 - PubMed
1. Pilotto A, di Schiano Cola F, Premi E, Grasso R, Turrone R, Gipponi S et al (2019) Extrastriatal dopaminergic and serotonergic pathways in Parkinson’s disease and in dementia with Lewy bodies: a 123 I-FP-CIT SPECT study. Eur J Nucl Med Mol Imaging 46:1642–51 - PubMed
1. Markello RD, Arnatkeviciute A, Poline J-B, Fulcher BD, Fornito A, Misic B (2021) Standardizing workflows in imaging transcriptomics with the abagen toolbox. Elife 10:e72129 - PMC - PubMed
1. Boylan LS, Chiò A (2019) Divining progression in Parkinson disease with a blood test: NfL. Neurology 93(11):471–472 - PubMed

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[1] Espay AJ, Schwarzschild MA, Tanner CM, Fernandez HH, Simon DK, Leverenz JB et al (2017) Biomarker-driven phenotyping in Parkinson’s disease: a translational missing link in disease-modifying clinical trials. Mov Disord 32:319–324 - PMC - PubMed

[2] Espay AJ, Schwarzschild MA, Tanner CM, Fernandez HH, Simon DK, Leverenz JB et al (2017) Biomarker-driven phenotyping in Parkinson’s disease: a translational missing link in disease-modifying clinical trials. Mov Disord 32:319–324 - PMC - PubMed

[3] Fereshtehnejad S-M, Romenets SR, Anang JBM, Latreille V, Gagnon J-F, Postuma RB (2015) New clinical subtypes of Parkinson disease and their longitudinal progression: a prospective cohort comparison with other phenotypes. JAMA Neurol 72:863–873 - PubMed

[4] Fereshtehnejad S-M, Romenets SR, Anang JBM, Latreille V, Gagnon J-F, Postuma RB (2015) New clinical subtypes of Parkinson disease and their longitudinal progression: a prospective cohort comparison with other phenotypes. JAMA Neurol 72:863–873 - PubMed

[5] Pilotto A, di Schiano Cola F, Premi E, Grasso R, Turrone R, Gipponi S et al (2019) Extrastriatal dopaminergic and serotonergic pathways in Parkinson’s disease and in dementia with Lewy bodies: a 123 I-FP-CIT SPECT study. Eur J Nucl Med Mol Imaging 46:1642–51 - PubMed

[6] Pilotto A, di Schiano Cola F, Premi E, Grasso R, Turrone R, Gipponi S et al (2019) Extrastriatal dopaminergic and serotonergic pathways in Parkinson’s disease and in dementia with Lewy bodies: a 123 I-FP-CIT SPECT study. Eur J Nucl Med Mol Imaging 46:1642–51 - PubMed

[7] Markello RD, Arnatkeviciute A, Poline J-B, Fulcher BD, Fornito A, Misic B (2021) Standardizing workflows in imaging transcriptomics with the abagen toolbox. Elife 10:e72129 - PMC - PubMed

[8] Markello RD, Arnatkeviciute A, Poline J-B, Fulcher BD, Fornito A, Misic B (2021) Standardizing workflows in imaging transcriptomics with the abagen toolbox. Elife 10:e72129 - PMC - PubMed

[9] Boylan LS, Chiò A (2019) Divining progression in Parkinson disease with a blood test: NfL. Neurology 93(11):471–472 - PubMed

[10] Boylan LS, Chiò A (2019) Divining progression in Parkinson disease with a blood test: NfL. Neurology 93(11):471–472 - PubMed

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Plasma NfL, GFAP, amyloid, and p-tau species as Prognostic biomarkers in Parkinson's disease

Affiliations

Plasma NfL, GFAP, amyloid, and p-tau species as Prognostic biomarkers in Parkinson's disease

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