Recent studies have elucidated various molecular mechanisms underlying neurodegenerative diseases, particularly focusing on proteins such as alpha-synuclein and tau. A novel missense variant in the SNCA gene, associated with atypical neuropathological features, was identified in a patient with a complex neurodegenerative disorder, highlighting the genetic diversity in Parkinson's disease (ref: Brücke doi.org/10.1186/s13024-025-00889-y/). Additionally, tau hyperphosphorylation, a hallmark of tauopathies like Alzheimer's disease, was shown to occur physiologically during mammalian hibernation, suggesting a reversible model for studying tau metabolism and its implications in neurodegeneration (ref: Brum doi.org/10.1007/s00401-025-02930-2/). Furthermore, targeting lipid droplets in FUS-linked amyotrophic lateral sclerosis (ALS) demonstrated a potential therapeutic avenue, as it mitigated neuronal and astrocytic lipotoxicity, emphasizing the metabolic shifts in ALS (ref: Marcadet doi.org/10.1093/brain/). The role of TDP-43 in ALS and frontotemporal lobar degeneration was also explored, with in vivo self-assembled siRNAs showing promise in ameliorating neurological pathology (ref: Wu doi.org/10.1093/brain/). Lastly, telomere-driven senescence was found to accelerate tau pathology and neuroinflammation in a tauopathy mouse model, linking aging to neurodegenerative processes (ref: Palomares doi.org/10.1186/s40478-025-02118-5/).

The tumor microenvironment (TME) plays a crucial role in the progression and treatment response of various cancers, particularly in pediatric low-grade gliomas (pLGGs) and IDH-mutant astrocytomas. A spatial map of myeloid populations in pLGGs revealed that myeloid cells, including resident microglia and bone marrow-derived macrophages, dominate the TME, especially in optic pathway tumors, which could inform therapeutic strategies (ref: Andrade doi.org/10.1038/s41590-025-02268-7/). In IDH-mutant astrocytomas, a protein-based classification identified an immune-hot subtype associated with poorer prognosis, emphasizing the need for tailored treatment approaches (ref: Tang doi.org/10.1016/j.ccell.2025.08.006/). Furthermore, the Pathology Image Characterization Tool (PICTURE) system was developed to differentiate glioblastoma from its mimics, enhancing diagnostic accuracy in central nervous system cancers (ref: Zhao doi.org/10.1038/s41467-025-64249-6/). The role of border-associated macrophages in pneumococcal meningitis was also investigated, revealing that their depletion worsened disease outcomes, underscoring their importance in immune responses (ref: Dyckhoff-Shen doi.org/10.1186/s40478-025-02126-5/). Lastly, a user-friendly R package for cumulative copy number variation analyses was introduced, facilitating large-scale genomic studies in tumor diagnostics (ref: Gocke doi.org/10.1186/s12859-025-06269-z/).

Genetic and epigenetic alterations significantly influence the behavior and treatment responses of central nervous system (CNS) tumors. A multi-institutional cohort analysis revealed that TERT promoter mutations in meningiomas correlate with patient outcomes, with distinct demographic patterns observed between TERTp-mutant and wildtype cases (ref: Groff doi.org/10.1016/S1470-2045(25)00422-X/). In glioblastomas, tumor heterogeneity driven by NF1 mutations was shown to affect the efficacy of MEK inhibitors, highlighting the complexity of treatment responses in genetically diverse tumors (ref: Pan doi.org/10.1172/jci.insight.192658/). Additionally, an in silico purification framework improved DNA methylation-based classification rates of pediatric low-grade gliomas, aiding in the molecular diagnosis of previously non-classifiable cases (ref: Jürgensen doi.org/10.1007/s00401-025-02939-7/). The differences in TDP-43 pathology between pure LATE-NC and LATE-NC coexisting with Alzheimer's disease were also characterized, revealing distinct aggregate compositions and nuclear clearance patterns (ref: Tomé doi.org/10.1007/s00401-025-02929-9/). Lastly, comprehensive molecular profiling of cribriform tumors identified recurrent genetic alterations, enhancing diagnostic precision (ref: Sohier doi.org/10.1016/j.modpat.2025.100889/).

Advancements in diagnostic methodologies are crucial for improving the accuracy of neuropathological assessments. A study on frontotemporal dementia (FTD) patient-derived iPSC neurons demonstrated pathological hallmarks and synaptic dysfunction, providing insights into the disease's underlying mechanisms (ref: Huber doi.org/10.1038/s41380-025-03272-x/). In the context of seronegative myasthenia gravis, next-generation sequencing was employed to screen for congenital myasthenic syndromes, revealing significant clinical implications for diagnosis and treatment (ref: Krenn doi.org/10.1212/WNL.0000000000214177/). The cIMPACT-NOW update proposed adaptations to diagnostic criteria for diffuse high-grade gliomas, emphasizing the need for careful classification to avoid misdiagnosis (ref: Wesseling doi.org/10.1111/bpa.70035/). Moreover, deep sequencing of chronic subdural hematomas suggested bacterial involvement in recurrences, highlighting the importance of understanding underlying pathologies in recurrent cases (ref: Mohr doi.org/10.1227/neu.0000000000003754/). High-resolution mapping of glutamate and glutamine in gliomas using 7-T MR spectroscopic imaging provided valuable metabolic insights that could inform treatment strategies (ref: Hangel doi.org/10.1148/rycan.240494/).

The exploration of pathological features and biomarkers in CNS disorders has revealed critical insights into disease mechanisms and potential therapeutic targets. The role of border-associated macrophages in pneumococcal meningitis was highlighted, where their pharmacologic depletion exacerbated disease progression, indicating their protective role in inflammation (ref: Dyckhoff-Shen doi.org/10.1186/s40478-025-02126-5/). Additionally, a systematic review of iatrogenic cerebral amyloid angiopathy cases provided new insights into its pathophysiology, suggesting a link between surgical interventions and amyloid deposition (ref: Sofia Costa doi.org/10.1186/s42466-025-00423-x/). A meta-analysis of UBQLN2 variants in ALS and frontotemporal dementia revealed significant sex differences in disease presentation, which could enhance risk prediction and management strategies (ref: Thumbadoo doi.org/10.1016/j.nbd.2025.107127/). Furthermore, the development of a user-friendly R package for cumulative copy number variation analyses has improved the scalability of genomic studies, facilitating better tumor diagnostics (ref: Gocke doi.org/10.1186/s12859-025-06269-z/). Lastly, downregulation of TCF19 and ATAD2 was associated with endothelial cell cycle arrest in heart failure, linking transcriptional regulation to disease progression (ref: Erny doi.org/10.1007/s00395-025-01139-4/).

Neuroinflammation and cellular responses play pivotal roles in CNS disorders, influencing disease progression and therapeutic outcomes. Early microglia progenitors were shown to colonize the embryonic CNS through integrin-mediated migration, shedding light on the developmental origins of microglia and their roles in neuroinflammatory responses (ref: Petry doi.org/10.1016/j.devcel.2025.08.012/). The impact of pharmacologic depletion of border-associated macrophages in pneumococcal meningitis was investigated, revealing that their absence worsened disease outcomes, highlighting their importance in mediating immune responses (ref: Dyckhoff-Shen doi.org/10.1186/s40478-025-02126-5/). Additionally, the development of a user-friendly R package for cumulative copy number variation analyses has enhanced the ability to interpret large-scale genomic data, facilitating better understanding of tumor biology (ref: Gocke doi.org/10.1186/s12859-025-06269-z/). These findings underscore the complex interplay between neuroinflammation and cellular responses in the context of CNS disorders, suggesting potential therapeutic targets for intervention.

Molecular profiling has significant clinical implications for the diagnosis and treatment of CNS tumors. A study on canine cognitive dysfunction established the dog as a translational model for Alzheimer's disease, facilitating the development of a longitudinal research platform for studying disease mechanisms and therapeutic interventions (ref: McGrath doi.org/10.1002/alz.70630/). In a retrospective study of meningiomas, the integration of molecular insights from cIMPACT-NOW updates improved prognostication and understanding of tumor behavior, addressing limitations of traditional histopathological grading (ref: Ali doi.org/10.3389/fonc.2025.1648953/). High-resolution mapping of glutamate and glutamine in gliomas using 7-T MR spectroscopic imaging provided valuable metabolic insights that could inform treatment strategies (ref: Hangel doi.org/10.1148/rycan.240494/). The investigation of chronic subdural hematomas suggested bacterial involvement in recurrences, emphasizing the need for comprehensive diagnostic approaches (ref: Mohr doi.org/10.1227/neu.0000000000003754/). Lastly, hyperspectral imaging was explored for quantifying DKK-3 expression in oropharyngeal carcinoma, demonstrating its potential as a diagnostic tool (ref: Mittermair doi.org/10.3390/bioengineering12090971/).