TY - JOUR
T1 - Exploring brain-glioma interaction
T2 - Effect of neuroligin-3 expression on neurocognitive functioning is independent from epilepsy
AU - Krijnen, Eva A
AU - van Kessel, Emma
AU - Mühlebner, Angelika
AU - van Kempen, Sven
AU - Van Hecke, Wim
AU - van Zandvoort, Martine J E
AU - Robe, Pierre A
AU - Snijders, Tom J
N1 - Publisher Copyright:
© The Author(s) 2026. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
PY - 2026/1
Y1 - 2026/1
N2 - BACKGROUND: Neurocognitive deficits are common in patients with diffuse glioma, compromising quality of life and prognosis. Neuroligin-3 is a postsynaptic activity-dependent protein, considered a key component of brain-glioma interactions, specifically at neurogliomal synapses. Neuroligin-3 may modulate neuronal and epileptic activity, contributing to both tumor growth and cognitive deficits. We aimed to investigate the relationship between intratumoral neuroligin-3 expression and neurocognitive functioning (NCF) in diffuse glioma patients, and to determine whether epilepsy modifies this relationship.METHODS: In this single-center retrospective study, adult patients with grades 2-4 diffuse glioma underwent neuropsychological assessment prior to awake surgery. Tissue microarray analysis was used to assess intratumoral neuroligin-3 expression. We examined the relation between NCF (attention and executive functioning, memory, language, visuospatial functioning and psychomotor speed) and neuroligin-3 expression, using multivariable logistic regression models adjusting for tumor grade, location and volume. Additionally, presence of epilepsy and its interaction term with neuroligin-3 expression were added to separate models.RESULTS: In total, 101 patients were included for analyses. Neuroligin-3 showed a protective effect on memory performance in all patients, not modified by epilepsy. Patients with neuroligin-3-positive high-grade and isocitrate dehydrogenase (IDH)-wild type glioma have a decreased risk of memory and attention and executive functioning deficits, again not modified by epilepsy. In low-grade and IDH-mutant glioma patients, neuroligin-3 expression was not associated with NCF.CONCLUSIONS: Intratumoral neuroligin-3 expression is an independent determinant of NCF, especially in the domain memory and in high-grade and IDH-wild type glioma. This protective effect was not modified by presence of epilepsy.
AB - BACKGROUND: Neurocognitive deficits are common in patients with diffuse glioma, compromising quality of life and prognosis. Neuroligin-3 is a postsynaptic activity-dependent protein, considered a key component of brain-glioma interactions, specifically at neurogliomal synapses. Neuroligin-3 may modulate neuronal and epileptic activity, contributing to both tumor growth and cognitive deficits. We aimed to investigate the relationship between intratumoral neuroligin-3 expression and neurocognitive functioning (NCF) in diffuse glioma patients, and to determine whether epilepsy modifies this relationship.METHODS: In this single-center retrospective study, adult patients with grades 2-4 diffuse glioma underwent neuropsychological assessment prior to awake surgery. Tissue microarray analysis was used to assess intratumoral neuroligin-3 expression. We examined the relation between NCF (attention and executive functioning, memory, language, visuospatial functioning and psychomotor speed) and neuroligin-3 expression, using multivariable logistic regression models adjusting for tumor grade, location and volume. Additionally, presence of epilepsy and its interaction term with neuroligin-3 expression were added to separate models.RESULTS: In total, 101 patients were included for analyses. Neuroligin-3 showed a protective effect on memory performance in all patients, not modified by epilepsy. Patients with neuroligin-3-positive high-grade and isocitrate dehydrogenase (IDH)-wild type glioma have a decreased risk of memory and attention and executive functioning deficits, again not modified by epilepsy. In low-grade and IDH-mutant glioma patients, neuroligin-3 expression was not associated with NCF.CONCLUSIONS: Intratumoral neuroligin-3 expression is an independent determinant of NCF, especially in the domain memory and in high-grade and IDH-wild type glioma. This protective effect was not modified by presence of epilepsy.
U2 - 10.1093/noajnl/vdag123
DO - 10.1093/noajnl/vdag123
M3 - Article
C2 - 42291752
SN - 2632-2498
VL - 8
JO - Neuro-oncology advances
JF - Neuro-oncology advances
IS - 1
M1 - vdag123
ER -