Exploring brain-glioma interaction: effect of neuroligin-3 expression on neurocognitive functioning is independent from epilepsy
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ID: 313898
2026
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Abstract
Abstract 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 intra-tumoral neuroligin-3 expression and neurocognitive functioning in diffuse glioma patients, and to determine whether epilepsy modifies this relationship. Methods In this single-center retrospective study, adult patients with grade 2–4 diffuse glioma underwent neuropsychological assessment prior to awake surgery. Tissue microarray analysis was used to assess intra-tumoral neuroligin-3 expression. We examined the relation between neurocognitive functioning (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 neurocognitive functioning. Conclusions Intra-tumoral neuroligin-3 expression is an independent determinant of neurocognitive functioning, especially in the domain memory and in high-grade and IDH-wild type glioma. This protective effect was not modified by presence of epilepsy.
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| Authors | Eva A. Krijnen, Emma van Kessel, Angelika Mühlebner, Sven van Kempen, Wim Van Hecke, Martine J E Van Zandvoort, Pierre A Robe, Tom J. Snijders |
| Journal | Neuro-Oncology Advances |
| Year | 2026 |
| DOI |
10.1093/noajnl/vdag123
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| URL | |
| Keywords | Keywords not found |
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