Recent studies have significantly advanced our understanding of the molecular mechanisms underlying brain tumors, particularly gliomas and astrocytomas. A pivotal study characterized newly diagnosed astrocytoma, IDH-mutant, WHO grade 4 (Astro4), revealing that CDKN2A/B deletion, age, and the extent of resection are critical prognostic factors (ref: Lasica doi.org/10.1093/neuonc/). Another important contribution is the development of a unified nanopore-based assay that integrates intraoperative methylome classification with next-day comprehensive profiling, allowing for ultra-rapid tumor diagnosis and a paradigm shift in CNS tumor classification based on epigenetic signatures (ref: Deacon doi.org/10.1093/neuonc/). Furthermore, the creation of a single-cell and spatial atlas of IDH-wildtype glioblastoma has unveiled its cellular heterogeneity and spatial organization, providing a comprehensive resource for understanding this aggressive malignancy (ref: Ruiz-Moreno doi.org/10.1093/neuonc/). These studies collectively emphasize the importance of molecular profiling in the diagnosis and treatment of brain tumors, highlighting the potential for personalized therapeutic strategies based on genetic and epigenetic alterations.

Prognostic factors play a crucial role in the management of neuro-oncological conditions, particularly in gliomas and meningiomas. A comprehensive study on astrocytoma, IDH-mutant, WHO grade 4, identified CDKN2A/B deletions, patient age, and the extent of tumor resection as significant predictors of prognosis (ref: Lasica doi.org/10.1093/neuonc/). Additionally, research on recurrent WHO grade 1 meningiomas demonstrated that molecular profiling can stratify patients into risk groups, with those having intermediate/high-risk profiles showing markedly worse progression-free survival rates compared to low-risk counterparts (ref: Deng doi.org/10.1093/neuonc/). These findings underscore the necessity of integrating clinical, molecular, and radiological data to enhance prognostic accuracy and tailor treatment strategies. The identification of actionable mutations in adolescent and young adult high-grade gliomas further emphasizes the need for targeted therapies in this demographic, which has historically been underrepresented in clinical research (ref: Morfouace doi.org/10.1016/j.ejca.2025.115493/).

Innovative diagnostic approaches are transforming the landscape of neuro-oncology, particularly through the integration of advanced genomic technologies. The introduction of a nanopore-based assay for rapid tumor diagnosis exemplifies this shift, allowing for intraoperative methylome classification and expediting the diagnostic process (ref: Deacon doi.org/10.1093/neuonc/). Furthermore, the application of DNA methylation profiling has led to the identification of distinct methylation classes in neuroepithelial tumors, such as PATZ1-fused tumors, which exhibit significant morphological and radiological diversity (ref: Tauziède-Espariat doi.org/10.1186/s40478-025-02037-5/). Another study highlighted the utility of methylation arrays in risk stratification of meningiomas, demonstrating that combining WHO grade with molecular profiles can enhance predictions of early recurrence (ref: Ruiz doi.org/10.1111/nan.70018/). These advancements not only improve diagnostic accuracy but also pave the way for personalized treatment strategies based on individual tumor biology.

Research into neuropathology and neurodegenerative diseases has revealed critical insights into the mechanisms underlying conditions such as Alzheimer's disease and vanishing white matter. A study investigating the role of insulin signaling in microglia found that its loss impairs the cellular uptake of amyloid-beta, exacerbating neuroinflammatory responses and contributing to Alzheimer's-like pathology (ref: Chen doi.org/10.1073/pnas.2501527122/). Additionally, acute targeting of N-terminal tau protein in a mouse model demonstrated long-lasting benefits by reducing cognitive impairment and amyloid pathology, highlighting potential therapeutic avenues for Alzheimer's disease (ref: Latina doi.org/10.1186/s40478-025-02022-y/). Furthermore, the exploration of cell-specific Eif2b5 mutant mice has provided novel insights into the roles of macroglia in the development of vanishing white matter, emphasizing the need for a deeper understanding of cellular contributions to neurodegenerative processes (ref: Triñanes-Ramos doi.org/10.1093/brain/). These findings collectively underscore the complex interplay between molecular mechanisms and neuropathological changes in neurodegenerative diseases.

The landscape of therapeutic strategies in neuro-oncology is evolving, with a focus on personalized medicine and innovative clinical trials. A notable phase 2 trial investigated the efficacy of a chemotherapy-free neoadjuvant regimen combining pembrolizumab with trastuzumab and pertuzumab in HER2-enriched early breast cancer, demonstrating promising results in achieving pathological complete responses (ref: Kuemmel doi.org/10.1016/S1470-2045(25)00097-X/). In glioblastoma, the Advanced brain Tumor TheRApy Clinical Trial (ATTRACT) aims to personalize treatment through ex vivo drug screening, allowing for tailored therapeutic recommendations based on individual tumor responses (ref: Berghoff doi.org/10.1093/noajnl/). Additionally, the significance of CDKN2A status in gliomas has been highlighted, with various diagnostic techniques revealing its role as a surrogate marker for prognosis (ref: Tauziède-Espariat doi.org/10.1093/jnen/). These studies reflect a shift towards more individualized treatment approaches, emphasizing the importance of integrating molecular diagnostics into clinical practice to enhance patient outcomes.

Understanding cellular and molecular pathways in neuropathology is essential for unraveling the complexities of disorders such as autism spectrum disorder (ASD) and pediatric high-grade gliomas (pHGGs). A study on functional connectivity dynamics in ASD identified abnormal drivers of connectivity across developmental stages, linking these changes to underlying cellular and molecular mechanisms (ref: Li doi.org/10.1002/advs.202403801/). In pHGGs, a comprehensive transcriptomic analysis revealed significant differences in the immune landscape compared to adult gliomas, suggesting that therapeutic responses may differ due to these biological variances (ref: LaBelle doi.org/10.1016/j.xcrm.2025.102095/). Moreover, research on TDP-43 overexpression in the hypothalamus demonstrated its role in metabolic dysregulation and behavioral changes, providing insights into the neuropathological consequences of protein misfolding (ref: Bergh doi.org/10.1186/s40478-025-02018-8/). Collectively, these studies emphasize the importance of elucidating cellular pathways to inform therapeutic strategies and improve outcomes in neuro-oncological and neurodegenerative diseases.

The exploration of genetic and epigenetic alterations in CNS tumors has revealed critical insights into tumor biology and potential therapeutic targets. A study on progressive supranuclear palsy identified a novel risk locus in NFASC through a genome-wide association study, highlighting the genetic underpinnings of this rare tauopathy (ref: García-González doi.org/10.1038/s41431-025-01872-3/). Additionally, the characterization of PATZ1-fused tumors through DNA methylation profiling has established its distinct molecular class, which is associated with diverse morphological presentations (ref: Tauziède-Espariat doi.org/10.1186/s40478-025-02037-5/). Furthermore, the investigation of CDKN2A status in gliomas has underscored its significance as a prognostic marker, with various diagnostic techniques revealing its role in tumor stratification (ref: Tauziède-Espariat doi.org/10.1093/jnen/). These findings collectively emphasize the importance of integrating genetic and epigenetic analyses into clinical practice to enhance diagnostic accuracy and inform treatment decisions.