Plasma Neurofilament Light Chain Is Elevated in Adaptor Protein Complex 4-Related Hereditary Spastic Paraplegia

Alecu JE, Saffari A, Ziegler M, Jordan C, Tam A, Kim S, Leung E, Szczaluba K, Mierzewska H, King SD, Santorelli FM, Yoon G, Trombetta B, Kivisäkk P, Zhang B, Sahin M, Ebrahimi-Fakhari D (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Movement Disorders Wiley-Blackwell

Book Volume: 38

Pages Range: 1742-1750

Journal Issue: 9

DOI: 10.1002/mds.29524

Abstract

Background: Adaptor protein complex 4-associated hereditary spastic paraplegia (AP-4-HSP) is caused by pathogenic biallelic variants in AP4B1, AP4M1, AP4E1, and AP4S1. Objective: The aim was to explore blood markers of neuroaxonal damage in AP-4-HSP. Methods: Plasma neurofilament light chain (pNfL) and glial fibrillary acidic protein (GFAP) levels were measured in samples from patients and age- and sex-matched controls (NfL: n = 46 vs. n = 46; GFAP: n = 14 vs. n = 21) using single-molecule array assays. Patients' phenotypes were systematically assessed using the AP-4-HSP natural history study questionnaires, the Spastic Paraplegia Rating Scale, and the SPATAX disability score. Results: pNfL levels increased in AP-4-HSP patients, allowing differentiation from controls (Mann-Whitney U test: P = 3.0e-10; area under the curve = 0.87 with a 95% confidence interval of 0.80–0.94). Phenotypic cluster analyses revealed a subgroup of individuals with severe generalized-onset seizures and developmental stagnation, who showed differentially higher pNfL levels (Mann-Whitney U test between two identified clusters: P = 2.5e-6). Plasma GFAP levels were unchanged in patients with AP-4-HSP. Conclusions: pNfL is a potential disease marker in AP-4-HSP and can help differentiate between phenotypic subgroups. © 2023 International Parkinson and Movement Disorder Society.

Involved external institutions

Veterans Affairs Healthcare System Boston and Harvard Medical School US United States (USA) (US) Sozialpädiatrisches Zentrum Frankfurt Mitte DE Germany (DE) University of Manitoba CA Canada (CA) Wrocław Medical University / Uniwersytet Medyczny we Wrocławiu PL Poland (PL) Institute of Mother and Child / Instytut Matki I Dziecka PL Poland (PL) Texas Children's Hospital US United States (USA) (US) IRCCS Fondazione Stella Maris IT Italy (IT) The Hospital for Sick Children (SickKids) CA Canada (CA) Massachusetts General Hospital US United States (USA) (US)

How to cite

APA:

Alecu, J.E., Saffari, A., Ziegler, M., Jordan, C., Tam, A., Kim, S.,... Ebrahimi-Fakhari, D. (2023). Plasma Neurofilament Light Chain Is Elevated in Adaptor Protein Complex 4-Related Hereditary Spastic Paraplegia. Movement Disorders, 38(9), 1742-1750. https://doi.org/10.1002/mds.29524

MLA:

Alecu, Julian E., et al. "Plasma Neurofilament Light Chain Is Elevated in Adaptor Protein Complex 4-Related Hereditary Spastic Paraplegia." Movement Disorders 38.9 (2023): 1742-1750.

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