The advancements in molecular diagnostics have significantly impacted the classification of central nervous system (CNS) tumors, particularly with the WHO 2021 classification. The guideline by Sahm et al. emphasizes the importance of molecular characteristics as essential diagnostic criteria for gliomas, glioneuronal, and neuronal tumors, detailing various molecular methods for assessing diagnostic and prognostic markers (ref: Sahm doi.org/10.1093/neuonc/). In pediatric populations, Kolodziejczak et al. highlight the clinical outcomes of medulloblastoma patients with Li-Fraumeni syndrome, indicating a need for comprehensive clinical data to develop effective therapeutic strategies (ref: Kolodziejczak doi.org/10.1093/neuonc/). Furthermore, Deng et al. analyze recurrence probabilities in CNS WHO grade 2 meningiomas post-radiotherapy, revealing that while current classifications predict recurrence for most patients, some experience unexpected early recurrences, suggesting a gap in the predictive capabilities of existing models (ref: Deng doi.org/10.1093/noajnl/). Massimino et al. explore the optimization of reirradiation for relapsed medulloblastoma, emphasizing the need for tailored treatment approaches based on patient and tumor profiles (ref: Massimino doi.org/10.1007/s11060-023-04361-z/). Lastly, Gallus et al. introduce translational imaging techniques to assess innate inflammation in autoimmune limbic encephalitis, underscoring the need for novel biomarkers in clinical assessments (ref: Gallus doi.org/10.1126/sciadv.abq7595/).

Tumor heterogeneity remains a critical challenge in oncology, influencing treatment efficacy and patient outcomes. Katiyar et al. present a machine-learning model that quantifies intratumoral heterogeneity using PET-MRI data, demonstrating its potential to provide biologically relevant probability maps of tumor subtypes, which could enhance therapeutic strategies (ref: Katiyar doi.org/10.1038/s41551-023-01047-9/). In the context of non-Alzheimer's dementias, Kaivola et al. conduct a genome-wide structural variant analysis, identifying risk loci that may contribute to the understanding of Lewy body dementia and frontotemporal dementia, thus highlighting the genetic underpinnings of these conditions (ref: Kaivola doi.org/10.1016/j.xgen.2023.100316/). Prokoph et al. explore patient-derived xenograft models of ALK+ anaplastic large-cell lymphoma, revealing the promising therapeutic potential of brigatinib, especially in cases with CNS involvement, where traditional treatments have shown limited efficacy (ref: Prokoph doi.org/10.1111/bjh.18953/). Ng et al. provide a multi-institutional retrospective analysis of pediatric supratentorial tumors, reporting significant survival rates and emphasizing the importance of molecular annotation in treatment planning (ref: Ng doi.org/10.1093/noajnl/). Crary et al. review recent trends in neurodegeneration, emphasizing the need for balanced research approaches to address various disease categories and their implications for treatment outcomes (ref: Crary doi.org/10.17879/freeneuropathology-2022-3866/).

Research into neurodegenerative diseases has increasingly focused on identifying biomarkers and understanding underlying mechanisms. Ferreiro et al. suggest that gut microbiome composition may serve as an early indicator of preclinical Alzheimer's disease, highlighting the potential for microbiome-targeted interventions (ref: Ferreiro doi.org/10.1126/scitranslmed.abo2984/). Duchs et al. investigate the therapeutic potential of an AAV-mediated anti-aggregated α-synuclein antibody in a genetic model of α-synucleinopathies, demonstrating prolonged survival and offering insights into immunotherapeutic strategies for diseases like Parkinson's (ref: Duchs doi.org/10.1038/s41531-023-00542-9/). Inyang et al. conduct a systematic review on the effects of capsaicin on Alzheimer's disease, suggesting its neuroprotective properties and potential role in cognitive function enhancement (ref: Inyang doi.org/10.3390/ijms241210176/). Otsuka et al. explore the genetic architecture of suicidal behavior, revealing shared polygenic effects with psychiatric disorders, which may inform future interventions (ref: Otsuka doi.org/10.1017/S0033291721004700/). Mittelbronn et al. provide an update on neurooncology, emphasizing advancements in diagnostic tools that enhance the precision of tumor classification and treatment strategies (ref: Mittelbronn doi.org/10.17879/freeneuropathology-2023-4692/).

The interplay between inflammation and immune responses is crucial in understanding neuropathological conditions. Molina-Gonzalez et al. demonstrate that astrocyte-oligodendrocyte interactions play a vital role in CNS regeneration, revealing that astrocytes support oligodendrocyte survival through specific metabolic pathways, which could inform therapeutic approaches for demyelinating diseases (ref: Molina-Gonzalez doi.org/10.1038/s41467-023-39046-8/). Makdissi et al. systematically review factors influencing athlete retirement after sport-related concussions, emphasizing the need for evidence-based guidelines to protect athletes' long-term health (ref: Makdissi doi.org/10.1136/bjsports-2023-106815/). Reuss et al. investigate the consequences of Nbs1 and p53 inactivation in neural progenitors, linking these genetic alterations to the development of high-grade gliomas, which underscores the importance of genetic factors in tumorigenesis (ref: Reuss doi.org/10.1111/nan.12915/). Tauziède-Espariat et al. conduct a comprehensive analysis of infantile CNS tumors, identifying distinct molecular characteristics that differentiate infant-type gliomas from other tumor types, which may refine diagnostic criteria (ref: Tauziède-Espariat doi.org/10.1111/bpa.13182/). Vogt et al. compare HIV-associated and sporadic inclusion body myositis, revealing shared and distinct features that could inform treatment strategies (ref: Vogt doi.org/10.1007/s00415-023-11779-y/).

The exploration of genetic and epigenetic factors in CNS tumors has revealed critical insights into tumor biology and treatment responses. Makdissi et al. highlight the importance of understanding the genetic predispositions influencing athletes' decisions to retire from contact sports following concussions, which may have implications for CNS injury management (ref: Makdissi doi.org/10.1136/bjsports-2023-106815/). Kaivola et al. identify structural variants associated with non-Alzheimer's dementias, providing a genetic framework that may enhance understanding of these complex disorders (ref: Kaivola doi.org/10.1016/j.xgen.2023.100316/). Massimino et al. focus on optimizing reirradiation strategies for relapsed medulloblastoma, emphasizing the need for personalized treatment approaches based on genetic and molecular tumor profiles (ref: Massimino doi.org/10.1007/s11060-023-04361-z/). Prokoph et al. present findings from patient-derived xenograft models of ALK+ ALCL, demonstrating the potential of brigatinib in overcoming treatment resistance in CNS relapses (ref: Prokoph doi.org/10.1111/bjh.18953/). McKenzie et al. discuss the technical aspects of ex situ perfusion fixation for brain banking, which may enhance the preservation of genetic material for future research (ref: McKenzie doi.org/10.17879/freeneuropathology-2022-4368/).

The clinical implications of molecular findings in neuropathology are profound, influencing diagnosis, treatment, and patient management. Pinho et al. investigate sex-specific patterns of cerebral atrophy in patients with cerebral amyloid angiopathy, revealing neuroimaging markers that may aid in the differential diagnosis of dementia (ref: Pinho doi.org/10.3174/ajnr.A7900/). Tachida et al. explore the role of O-GalNAc glycosylation in the intracellular trafficking of APP and Aβ production, shedding light on potential therapeutic targets for Alzheimer's disease (ref: Tachida doi.org/10.1016/j.jbc.2023.104905/). McKenzie et al. also address the challenges of brain banking through perfusion fixation, emphasizing the need for high-quality tissue preservation for molecular studies (ref: McKenzie doi.org/10.17879/freeneuropathology-2022-4368/). Duchs et al. report on the efficacy of a new α-synuclein antibody in prolonging survival in models of α-synucleinopathies, indicating promising avenues for immunotherapy (ref: Duchs doi.org/10.1038/s41531-023-00542-9/). Kolodziejczak et al. highlight the clinical outcomes of pediatric medulloblastoma patients with Li-Fraumeni syndrome, stressing the need for tailored therapeutic strategies based on molecular data (ref: Kolodziejczak doi.org/10.1093/neuonc/).