% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Kessler:285033,
author = {Kessler, Christoph and Wilke, Carlo and Hengel, Holger and
Rattay, Tim W and Maleska Maceski, Aleksandra and Kuhle,
Jens and Schöls, Ludger and Schüle, Rebecca},
title = {{S}erum {N}f{L}, but not {GFAP}, differentiates primary
lateral sclerosis from adrenomyeloneuropathy and hereditary
spastic paraplegia type 4.},
journal = {Amyotrophic lateral sclerosis $\&$ frontotemporal
degeneration},
volume = {27},
number = {1-2},
issn = {2167-8421},
address = {Abingdon},
publisher = {Taylor Francis Group},
reportid = {DZNE-2026-00158},
pages = {110 - 117},
year = {2026},
abstract = {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, $95\%$ CI 0.67-0.98)
and-slightly less accurate-from AMN (AUC 0.77, $95\%$ CI
0.60-0.95). sGFAP z-scores did not differ significantly
between groups.Our study suggests that serum NfL, but not
GFAP, is a potential diagnostic biomarker in degenerative
UMN diseases and may help to differentiate PLS from pure and
complicated forms of HSP. Our results indicate that axonal
degeneration-the source of NfL release-is predominant over
astrocytic pathology-the source of GFAP release-in PLS, AMN,
and SPG4.},
keywords = {Humans / Male / Female / Middle Aged / Spastic Paraplegia,
Hereditary: blood / Spastic Paraplegia, Hereditary:
diagnosis / Neurofilament Proteins: blood / Glial Fibrillary
Acidic Protein: blood / Adult / Adrenoleukodystrophy: blood
/ Adrenoleukodystrophy: diagnosis / Biomarkers: blood /
Diagnosis, Differential / Aged / Young Adult / Cohort
Studies / Biomarker (Other) / GFAP (Other) / HSP (Other) /
NfL (Other) / PLS (Other) / Neurofilament Proteins (NLM
Chemicals) / Glial Fibrillary Acidic Protein (NLM Chemicals)
/ neurofilament protein L (NLM Chemicals) / Biomarkers (NLM
Chemicals) / GFAP protein, human (NLM Chemicals)},
cin = {AG Gasser / AG Schöls},
ddc = {610},
cid = {I:(DE-2719)1210000 / I:(DE-2719)5000005},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40961460},
doi = {10.1080/21678421.2025.2557936},
url = {https://pub.dzne.de/record/285033},
}