TY  - JOUR
AU  - Kessler, Christoph
AU  - Wilke, Carlo
AU  - Hengel, Holger
AU  - Rattay, Tim W
AU  - Maleska Maceski, Aleksandra
AU  - Kuhle, Jens
AU  - Schöls, Ludger
AU  - Schüle, Rebecca
TI  - Serum NfL, but not GFAP, differentiates primary lateral sclerosis from adrenomyeloneuropathy and hereditary spastic paraplegia type 4.
JO  - Amyotrophic lateral sclerosis & frontotemporal degeneration
VL  - 27
IS  - 1-2
SN  - 2167-8421
CY  - Abingdon
PB  - Taylor Francis Group
M1  - DZNE-2026-00158
SP  - 110 - 117
PY  - 2026
AB  - Neurodegenerative upper motor neuron (UMN) syndromes ranging from primary lateral sclerosis (PLS) to pure and complicated types of hereditary spastic paraplegia (HSP) remain challenging to differentiate clinically, especially in the early stages of disease. As they share the hallmark of spastic paraparesis, easily accessible biomarkers are warranted to facilitate an early diagnosis.We examined serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) as diagnostic biomarkers to differentiate PLS from HSP, represented by two paradigmatic subtypes: SPG4, the most common type of pure HSP, and adrenomyeloneuropathy (AMN), a common complicated form of HSP. In addition to sNfL and sGFAP raw levels, we used age-adjusted z-scores to account for age-related biomarker level increases.In our cohort of 18 PLS patients, 18 AMN patients, 25 SPG4 patients and 60 controls, sNfL z-scores were higher in PLS than in SPG4 (p < 0.001), AMN (p = 0.03), and controls (p < 0.001). Furthermore, sNfL z-scores allowed distinguishing PLS from SPG4 (AUC 0.82, 95
KW  - Humans
KW  - Male
KW  - Female
KW  - Middle Aged
KW  - Spastic Paraplegia, Hereditary: blood
KW  - Spastic Paraplegia, Hereditary: diagnosis
KW  - Neurofilament Proteins: blood
KW  - Glial Fibrillary Acidic Protein: blood
KW  - Adult
KW  - Adrenoleukodystrophy: blood
KW  - Adrenoleukodystrophy: diagnosis
KW  - Biomarkers: blood
KW  - Diagnosis, Differential
KW  - Aged
KW  - Young Adult
KW  - Cohort Studies
KW  - Biomarker (Other)
KW  - GFAP (Other)
KW  - HSP (Other)
KW  - NfL (Other)
KW  - PLS (Other)
KW  - Neurofilament Proteins (NLM Chemicals)
KW  - Glial Fibrillary Acidic Protein (NLM Chemicals)
KW  - neurofilament protein L (NLM Chemicals)
KW  - Biomarkers (NLM Chemicals)
KW  - GFAP protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40961460
DO  - DOI:10.1080/21678421.2025.2557936
UR  - https://pub.dzne.de/record/285033
ER  -