Increased Serum Neurofilament Light Chain Levels in Parkinson's Disease Patients Carrying the p.A53T SNCA Mutation: Data from the Parkinson's Progression Markers Initiative Study

Nikolaos Papagiannakis; Christos Koros; Athina Maria Simitsi; Leonidas Stefanis; Kenneth Marek; Tanya Simuni; Andrew Siderowf; Caroline Tanner; Thomas F. Tropea; Tatiana Foroud; Lana Chahine; Brit Mollenhauer; Kalpana Merchant; Douglas Galasko; Christopher Coffey; Kathleen Poston; Roseanne Dobkin; Ethan Brown; Roy Alcalay; Dan Weintraub; Emily Flagg; Kimberly Fabrizio; Susan Bressman; Cornelis Blauwendraat; Paola Casalin; Sonya Dumanis; Raymond James; Karl Kieburtz; Sneha Mantri; Werner Poewe; Michael Schwarzschild; John Seibyl; David Standaert; Duygu Tosun-Turgut; Sohini Chowdhury; Jamie Eberling; Mark Frasier; Leslie Kirsch; Katie Kopil; Maggie Kuhl; Alyssa O'Grady; Todd Sherer; Tawny Willson; Tanya Simuni; Bridget McMahon; Craig Stanley; Kim Fabrizio; Dixie Ecklund; Sonja Jonsdottir; Claire Pauly; and The Parkinson's Progression Markers Initiative

doi:10.1002/mds.70236

Increased Serum Neurofilament Light Chain Levels in Parkinson's Disease Patients Carrying the p.A53T SNCA Mutation: Data from the Parkinson's Progression Markers Initiative Study

Nikolaos Papagiannakis^*
, Christos Koros
, Athina Maria Simitsi
, Leonidas Stefanis
, Kenneth Marek
, Tanya Simuni
, Andrew Siderowf
, Caroline Tanner
, Thomas F. Tropea
, Tatiana Foroud
, Lana Chahine
, Brit Mollenhauer
, Kalpana Merchant
, Douglas Galasko
, Christopher Coffey
, Kathleen Poston
, Roseanne Dobkin
, Ethan Brown
, Roy Alcalay
, Dan Weintraub

Emily Flagg, Kimberly Fabrizio, Susan Bressman, Cornelis Blauwendraat, Paola Casalin, Sonya Dumanis, Raymond James, Karl Kieburtz, Sneha Mantri, Werner Poewe, Michael Schwarzschild, John Seibyl, David Standaert, Duygu Tosun-Turgut, Sohini Chowdhury, Jamie Eberling, Mark Frasier, Leslie Kirsch, Katie Kopil, Maggie Kuhl, Alyssa O'Grady, Todd Sherer, Tawny Willson, Tanya Simuni, Bridget McMahon, Craig Stanley, Kim Fabrizio, Dixie Ecklund, Sonja Jonsdottir, Claire Pauly, and The Parkinson's Progression Markers Initiative

^*Corresponding author for this work

Transversal Translational Medicine

Research output: Contribution to journal › Article › Research › peer-review

Abstract

BACKGROUND: Serum neurofilament light chain (NfL) levels, a marker of axonal damage, are generally elevated in neurodegenerative conditions, but results in idiopathic Parkinson's disease (iPD) have been inconsistent. The p.A53T SNCA mutation usually leads to a severe form of PD.

OBJECTIVE: The aim of this work was to assess the possible use of serum NfL as a marker of ongoing neurodegeneration in A53T-PD.

METHODS: Using a propensity score matching-based technique with data from the Parkinson's Progression Markers Initiative, we matched, in a 3:1 ratio, A53T-PD participants to iPD patients and healthy control subjects (HCs) by age and disease duration, where applicable.

RESULTS: After matching, 18 A53T-PD, 54 iPD, and 54 HC subjects were analyzed. Serum NfL was higher in A53T-PD (9.82 [8.02-18.1] pg/ml) compared with HCs (7.54 [5.76-10.1], P = 0.008) or iPD patients (8.59 [6.86-11.1], P = 0.077) (overall P = 0.049).

CONCLUSIONS: A53T-PD patients have high NfL levels, which could potentially be used as an outcome in clinical trials with disease-modifying agents. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Original language	English
Number of pages	6
Journal	Movement Disorders
DOIs	https://doi.org/10.1002/mds.70236
Publication status	Published - 23 Feb 2026

Keywords

Parkinson's disease
neurofilament

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10.1002/mds.70236Licence: CC BY-NC-ND

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Papagiannakis, N., Koros, C., Simitsi, A. M., Stefanis, L., Marek, K., Simuni, T., Siderowf, A., Tanner, C., Tropea, T. F., Foroud, T., Chahine, L., Mollenhauer, B., Merchant, K., Galasko, D., Coffey, C., Poston, K., Dobkin, R., Brown, E., Alcalay, R., ... and The Parkinson's Progression Markers Initiative (2026). Increased Serum Neurofilament Light Chain Levels in Parkinson's Disease Patients Carrying the p.A53T SNCA Mutation: Data from the Parkinson's Progression Markers Initiative Study. Movement Disorders. https://doi.org/10.1002/mds.70236

@article{37f00f9d66fc443b84ecd1a38b9163cc,

title = "Increased Serum Neurofilament Light Chain Levels in Parkinson's Disease Patients Carrying the p.A53T SNCA Mutation: Data from the Parkinson's Progression Markers Initiative Study",

abstract = "BACKGROUND: Serum neurofilament light chain (NfL) levels, a marker of axonal damage, are generally elevated in neurodegenerative conditions, but results in idiopathic Parkinson's disease (iPD) have been inconsistent. The p.A53T SNCA mutation usually leads to a severe form of PD.OBJECTIVE: The aim of this work was to assess the possible use of serum NfL as a marker of ongoing neurodegeneration in A53T-PD.METHODS: Using a propensity score matching-based technique with data from the Parkinson's Progression Markers Initiative, we matched, in a 3:1 ratio, A53T-PD participants to iPD patients and healthy control subjects (HCs) by age and disease duration, where applicable.RESULTS: After matching, 18 A53T-PD, 54 iPD, and 54 HC subjects were analyzed. Serum NfL was higher in A53T-PD (9.82 [8.02-18.1] pg/ml) compared with HCs (7.54 [5.76-10.1], P = 0.008) or iPD patients (8.59 [6.86-11.1], P = 0.077) (overall P = 0.049).CONCLUSIONS: A53T-PD patients have high NfL levels, which could potentially be used as an outcome in clinical trials with disease-modifying agents. {\textcopyright} 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.",

keywords = "Parkinson's disease, neurofilament",

author = "Nikolaos Papagiannakis and Christos Koros and Simitsi, \{Athina Maria\} and Leonidas Stefanis and Kenneth Marek and Tanya Simuni and Andrew Siderowf and Caroline Tanner and Tropea, \{Thomas F.\} and Tatiana Foroud and Lana Chahine and Brit Mollenhauer and Kalpana Merchant and Douglas Galasko and Christopher Coffey and Kathleen Poston and Roseanne Dobkin and Ethan Brown and Roy Alcalay and Dan Weintraub and Emily Flagg and Kimberly Fabrizio and Susan Bressman and Cornelis Blauwendraat and Paola Casalin and Sonya Dumanis and Raymond James and Karl Kieburtz and Sneha Mantri and Werner Poewe and Michael Schwarzschild and John Seibyl and David Standaert and Duygu Tosun-Turgut and Sohini Chowdhury and Jamie Eberling and Mark Frasier and Leslie Kirsch and Katie Kopil and Maggie Kuhl and Alyssa O'Grady and Todd Sherer and Tawny Willson and Tanya Simuni and Bridget McMahon and Craig Stanley and Kim Fabrizio and Dixie Ecklund and Sonja Jonsdottir and Claire Pauly and \{and The Parkinson's Progression Markers Initiative\}",

note = "Publisher Copyright: {\textcopyright} 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. ",

year = "2026",

month = feb,

day = "23",

doi = "10.1002/mds.70236",

language = "English",

journal = "Movement Disorders",

issn = "0885-3185",

publisher = "John Wiley \& Sons Inc.",

}

Papagiannakis, N, Koros, C, Simitsi, AM, Stefanis, L, Marek, K, Simuni, T, Siderowf, A, Tanner, C, Tropea, TF, Foroud, T, Chahine, L, Mollenhauer, B, Merchant, K, Galasko, D, Coffey, C, Poston, K, Dobkin, R, Brown, E, Alcalay, R, Weintraub, D, Flagg, E, Fabrizio, K, Bressman, S, Blauwendraat, C, Casalin, P, Dumanis, S, James, R, Kieburtz, K, Mantri, S, Poewe, W, Schwarzschild, M, Seibyl, J, Standaert, D, Tosun-Turgut, D, Chowdhury, S, Eberling, J, Frasier, M, Kirsch, L, Kopil, K, Kuhl, M, O'Grady, A, Sherer, T, Willson, T, Simuni, T, McMahon, B, Stanley, C, Fabrizio, K, Ecklund, D, Jonsdottir, S , Pauly, C & and The Parkinson's Progression Markers Initiative 2026, 'Increased Serum Neurofilament Light Chain Levels in Parkinson's Disease Patients Carrying the p.A53T SNCA Mutation: Data from the Parkinson's Progression Markers Initiative Study', Movement Disorders. https://doi.org/10.1002/mds.70236

TY - JOUR

T1 - Increased Serum Neurofilament Light Chain Levels in Parkinson's Disease Patients Carrying the p.A53T SNCA Mutation

T2 - Data from the Parkinson's Progression Markers Initiative Study

AU - Papagiannakis, Nikolaos

AU - Koros, Christos

AU - Simitsi, Athina Maria

AU - Stefanis, Leonidas

AU - Marek, Kenneth

AU - Simuni, Tanya

AU - Siderowf, Andrew

AU - Tanner, Caroline

AU - Tropea, Thomas F.

AU - Foroud, Tatiana

AU - Chahine, Lana

AU - Mollenhauer, Brit

AU - Merchant, Kalpana

AU - Galasko, Douglas

AU - Coffey, Christopher

AU - Poston, Kathleen

AU - Dobkin, Roseanne

AU - Brown, Ethan

AU - Alcalay, Roy

AU - Weintraub, Dan

AU - Flagg, Emily

AU - Fabrizio, Kimberly

AU - Bressman, Susan

AU - Blauwendraat, Cornelis

AU - Casalin, Paola

AU - Dumanis, Sonya

AU - James, Raymond

AU - Kieburtz, Karl

AU - Mantri, Sneha

AU - Poewe, Werner

AU - Schwarzschild, Michael

AU - Seibyl, John

AU - Standaert, David

AU - Tosun-Turgut, Duygu

AU - Chowdhury, Sohini

AU - Eberling, Jamie

AU - Frasier, Mark

AU - Kirsch, Leslie

AU - Kopil, Katie

AU - Kuhl, Maggie

AU - O'Grady, Alyssa

AU - Sherer, Todd

AU - Willson, Tawny

AU - Simuni, Tanya

AU - McMahon, Bridget

AU - Stanley, Craig

AU - Fabrizio, Kim

AU - Ecklund, Dixie

AU - Jonsdottir, Sonja

AU - Pauly, Claire

AU - and The Parkinson's Progression Markers Initiative

PY - 2026/2/23

Y1 - 2026/2/23

N2 - BACKGROUND: Serum neurofilament light chain (NfL) levels, a marker of axonal damage, are generally elevated in neurodegenerative conditions, but results in idiopathic Parkinson's disease (iPD) have been inconsistent. The p.A53T SNCA mutation usually leads to a severe form of PD.OBJECTIVE: The aim of this work was to assess the possible use of serum NfL as a marker of ongoing neurodegeneration in A53T-PD.METHODS: Using a propensity score matching-based technique with data from the Parkinson's Progression Markers Initiative, we matched, in a 3:1 ratio, A53T-PD participants to iPD patients and healthy control subjects (HCs) by age and disease duration, where applicable.RESULTS: After matching, 18 A53T-PD, 54 iPD, and 54 HC subjects were analyzed. Serum NfL was higher in A53T-PD (9.82 [8.02-18.1] pg/ml) compared with HCs (7.54 [5.76-10.1], P = 0.008) or iPD patients (8.59 [6.86-11.1], P = 0.077) (overall P = 0.049).CONCLUSIONS: A53T-PD patients have high NfL levels, which could potentially be used as an outcome in clinical trials with disease-modifying agents. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

AB - BACKGROUND: Serum neurofilament light chain (NfL) levels, a marker of axonal damage, are generally elevated in neurodegenerative conditions, but results in idiopathic Parkinson's disease (iPD) have been inconsistent. The p.A53T SNCA mutation usually leads to a severe form of PD.OBJECTIVE: The aim of this work was to assess the possible use of serum NfL as a marker of ongoing neurodegeneration in A53T-PD.METHODS: Using a propensity score matching-based technique with data from the Parkinson's Progression Markers Initiative, we matched, in a 3:1 ratio, A53T-PD participants to iPD patients and healthy control subjects (HCs) by age and disease duration, where applicable.RESULTS: After matching, 18 A53T-PD, 54 iPD, and 54 HC subjects were analyzed. Serum NfL was higher in A53T-PD (9.82 [8.02-18.1] pg/ml) compared with HCs (7.54 [5.76-10.1], P = 0.008) or iPD patients (8.59 [6.86-11.1], P = 0.077) (overall P = 0.049).CONCLUSIONS: A53T-PD patients have high NfL levels, which could potentially be used as an outcome in clinical trials with disease-modifying agents. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

KW - Parkinson's disease

KW - neurofilament

UR - https://www.scopus.com/pages/publications/105032477416

UR - https://pubmed.ncbi.nlm.nih.gov/41730696/

U2 - 10.1002/mds.70236

DO - 10.1002/mds.70236

M3 - Article

C2 - 41730696

AN - SCOPUS:105032477416

SN - 0885-3185

JO - Movement Disorders

JF - Movement Disorders

ER -

Increased Serum Neurofilament Light Chain Levels in Parkinson's Disease Patients Carrying the p.A53T SNCA Mutation: Data from the Parkinson's Progression Markers Initiative Study

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Keywords

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