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@ARTICLE{Halbgebauer:286093,
author = {Halbgebauer, Steffen and Winger, Niklas and Elmas, Zeynep
and Fazeli, Badrieh and Bachhuber, Franziska and Erhart,
Deborah K and Soylu, Önder and Klassen, Paula and Senel,
Makbule and Dorst, Johannes and Haeusler, Karl Georg and
Weishaupt, Jochen H and Otto, Markus and Tumani, Hayrettin},
title = {{D}istinct cerebrospinal fluid profiles of astrocytic
aquaporin-4 and {GFAP} in neuroinflammatory disorders.},
journal = {Neurobiology of disease},
volume = {222},
issn = {0969-9961},
address = {[Amsterdam]},
publisher = {Elsevier},
reportid = {DZNE-2026-00389},
pages = {107351},
year = {2026},
abstract = {Aquaporin 4 (AQP4), a water channel expressed in astrocytic
end feet forming the blood brain barrier, is predominantly
expressed in the central nervous system. Cerebrospinal fluid
(CSF) AQP4 has now been suggested as a possible fluid
biomarker in Alzheimer's disease. However, its diagnostic
potential in primary neuroinflammatory diseases, where also
AQP4 autoantibodies can circulate, has so far not been
studied. We investigated the CSF of 301 patients for AQP4
and GFAP using ELISA. The single-center cohort consisted of
patients with multiple sclerosis (n = 81), chronic
inflammatory demyelinating polyneuropathy (n = 23),
Guillain-Barré-Syndrome (n = 13), meningitis/ encephalitis
(Men/Enc) (n = 19), myelin oligodendrocyte glycoprotein
antibody disease (n = 6), neuromyelitis optica spectrum
disease (NMOSD) (n = 12), and non-immune mediated
polyneuropathy (NIP) patients (n = 49). 98 patients without
acute or chronic neuroinflammation and neurodegneration
served as controls. Both CSF AQP4 (r = 0.45 $(95\%CI:$
0.36-0.54), p < 0.0001) and GFAP (r = 0.4 $(95\%CI:$
0.30-0.49), p < 0.0001) correlated with age in the whole
cohort. CSF AQP4 levels were elevated in the NIP group
compared to control, MS and Men/Enc patients (p = 0.002, p =
0.029 and 0.005, respectively). When stratified further, the
hereditary NIP patients (n = 26) displayed the highest AQP4
levels of all groups. CSF GFAP was elevated in the AQP4
autoantibody positive NMOSD group but was not increased in
AQP4 autoantibody negative NMOSD patients. CSF AQP4 levels
were similar in both NMOSD groups. Combining AQP4 and GFAP
levels or calculating their ratio did not prominently
enhance diagnostic discrimination. The study highlights the
diagnostic potential of AQP4 as a fluid biomarker in
neurological conditions, especially in peripheral
neuropathies, while confirming GFAP as marker for astrocytic
injury in autoantibody positive NMOSD patients. Our findings
suggest that AQP4 and GFAP reflect different astrocytic
processes in neurological diseases.},
keywords = {Humans / Aquaporin 4: cerebrospinal fluid / Male / Female /
Middle Aged / Adult / Biomarkers: cerebrospinal fluid /
Astrocytes: metabolism / Glial Fibrillary Acidic Protein:
cerebrospinal fluid / Aged / Neuroinflammatory Diseases:
cerebrospinal fluid / Neuroinflammatory Diseases: diagnosis
/ Cohort Studies / Young Adult / Autoantibodies:
cerebrospinal fluid / Aquaporin 4 (Other) / Astrocytes
(Other) / Biomarker (Other) / Cerebrospinal fluid (Other) /
GFAP (Other) / Aquaporin 4 (NLM Chemicals) / AQP4 protein,
human (NLM Chemicals) / Biomarkers (NLM Chemicals) / Glial
Fibrillary Acidic Protein (NLM Chemicals) / GFAP protein,
human (NLM Chemicals) / Autoantibodies (NLM Chemicals)},
cin = {Clinical Study Center (Ulm)},
ddc = {570},
cid = {I:(DE-2719)5000077},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41831579},
doi = {10.1016/j.nbd.2026.107351},
url = {https://pub.dzne.de/record/286093},
}