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

Andrea Pilotto; Nicholas J Ashton; Alessandro Lupini; Beatrice Battaglio; Cinzia Zatti; Chiara Trasciatti; Stefano Gipponi; Elisabetta Cottini; Ilaria Grossi; Alessandro Salvi; Giuseppina de Petro; Marina Pizzi; Antonio Canale; Kaj Blennow; Henrik Zetterberg; Alessandro Padovani

doi:10.1007/s00415-024-12669-7

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

J Neurol. 2024 Dec;271(12):7537-7546. doi: 10.1007/s00415-024-12669-7. Epub 2024 Sep 9.

Authors

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.

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.

MeSH terms

Aged
Amyloid beta-Peptides* / blood
Biomarkers* / blood
Disease Progression*
Female
Follow-Up Studies
Glial Fibrillary Acidic Protein* / blood
Humans
Male
Middle Aged
Neurofilament Proteins* / blood
Parkinson Disease* / blood
Parkinson Disease* / diagnosis
Peptide Fragments / blood
Phosphorylation
Prognosis
Severity of Illness Index
tau Proteins* / blood

Substances

tau Proteins
Neurofilament Proteins
neurofilament protein L
Glial Fibrillary Acidic Protein
Biomarkers
Amyloid beta-Peptides
GFAP protein, human
amyloid beta-protein (1-42)
Peptide Fragments
MAPT protein, human

Abstract

MeSH terms

Substances

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