Research into the molecular mechanisms underlying neurodegenerative diseases has revealed critical insights, particularly regarding Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). A study comparing neuropathological changes in Alzheimer's patients treated with aducanumab versus untreated individuals highlighted the importance of amyloid β (Aβ) clearance and its correlation with amyloid-related imaging abnormalities (ARIA), suggesting that effective Aβ-targeting therapies could optimize treatment outcomes (ref: Boon doi.org/10.1016/S1474-4422(25)00313-8/). In ALS, the role of microglia and neuroinflammation was emphasized through the investigation of C9orf72 hexanucleotide repeat expansions, which were found to impair microglial responses, indicating a potential mechanism for disease progression (ref: Masrori doi.org/10.1038/s41593-025-02075-1/). Furthermore, the identification of novel differentially expressed genes in brain tissue from African American donors with AD has broadened the understanding of genetic factors influencing disease pathology, revealing 482 significant genes that could inform future therapeutic strategies (ref: Logue doi.org/10.1002/alz.70629/). Additionally, the regulation of tau protein by circular RNA circCwc27 was explored, linking shared pathogenic mechanisms between AD and type 2 diabetes mellitus, thereby highlighting the interconnectedness of metabolic and neurodegenerative disorders (ref: Fang doi.org/10.1186/s40708-025-00277-8/).

The molecular characterization of tumors, particularly in pediatric central nervous system cancers like medulloblastoma and ependymoma, has advanced significantly. An integrated transcriptomic analysis of 888 medulloblastoma and 370 ependymoma tumors revealed novel subtype-specific biology, enhancing the understanding of tumor heterogeneity and potential therapeutic targets (ref: Arora doi.org/10.1093/neuonc/). In the realm of neuroendocrine neoplasms (NEN), DNA methylation patterns were shown to be crucial for tracing the origin of these tumors, particularly in distinguishing primary hepatic NEN from metastases, which is vital for effective treatment strategies (ref: Goeppert doi.org/10.1038/s41467-025-65227-8/). Furthermore, the development of explainable AI for Gleason grading in prostate cancer represents a significant step towards improving diagnostic accuracy while maintaining clinical applicability (ref: Mittmann doi.org/10.1038/s41467-025-64712-4/). The characterization of diffuse leptomeningeal glioneuronal tumors (DLGNT) also provided insights into their clinical and molecular features, emphasizing the need for tailored treatment approaches (ref: Campanelli doi.org/10.1186/s40478-025-02100-1/). Lastly, methylation profiling has emerged as a diagnostic tool for Merkel cell carcinoma, aiding in the differentiation of this aggressive tumor from other neuroendocrine carcinomas (ref: Chantreau doi.org/10.1007/s00428-025-04271-7/).

Neuroinflammation and the immune response play pivotal roles in various neurological disorders, as evidenced by recent studies. The impact of C9orf72 hexanucleotide repeat expansions on microglial response in ALS was highlighted, demonstrating that these genetic alterations impair the innate immune response, potentially exacerbating disease progression (ref: Masrori doi.org/10.1038/s41593-025-02075-1/). Additionally, research into extracellular vesicles (EVs) has shown their potential as biomarkers for ischemic stroke, with alterations in EV RNA cargoes providing insights into stroke pathology and recovery following human neural stem cell therapy (ref: Chang doi.org/10.1002/mco2.70400/). The study of autonomy duration in patients with unresectable IDH wild-type glioblastomas revealed median durations of 7.7 months, underscoring the need for effective management strategies in this challenging cohort (ref: Harlay doi.org/10.1007/s11060-025-05250-3/). Furthermore, the exploration of post-infectious autoimmune disorders following SARS-CoV-2 infection illustrated the complex interplay between viral infections and neuroinflammatory responses, highlighting the necessity for comprehensive clinical evaluations in affected patients (ref: Umathum doi.org/10.1186/s42466-025-00436-6/).

The integration of molecular diagnostics into clinical practice has shown promise in improving patient outcomes across various neurological conditions. A study on diffuse midline gliomas in pediatric patients emphasized the correlation between molecular characteristics and clinical features, revealing that the presence of TP53 mutations and absence of MAPK pathway alterations were associated with worse outcomes (ref: Pfaff doi.org/10.1007/s00401-025-02945-9/). In Japan, the real-world adoption of lecanemab for Alzheimer's disease treatment highlighted infrastructure and reimbursement barriers, with 79% of specialists reporting wait times of three months or less for initial infusions, indicating a need for improved healthcare systems to facilitate timely treatment (ref: Sato doi.org/10.1002/alz.70652/). The role of re-resection in recurrent adult-type diffuse gliomas was also examined, revealing that 335 patients who underwent this procedure showed varied outcomes, emphasizing the importance of individualized treatment plans (ref: Cheng doi.org/10.1016/j.medj.2025.100891/). Additionally, recommendations for practical diagnostic strategies for adult-type diffuse gliomas were proposed, addressing the challenges faced in low-income settings regarding molecular testing implementation (ref: Santosh doi.org/10.1111/bpa.70046/). Lastly, the association of argyrophilic grain disease with cognitive decline and parkinsonism further underscores the relevance of molecular diagnostics in understanding and managing neurodegenerative disorders (ref: Arakawa doi.org/10.1093/braincomms/).

The exploration of genetic and epigenetic factors in neuropathology has unveiled significant insights into various neurological disorders. In the context of vanishing white matter, endogenous repair mechanisms were observed, suggesting that acute lesions can spontaneously resolve, highlighting the brain's capacity for self-repair (ref: Plug doi.org/10.1002/ana.78083/). The association of PIK3CA mutations with brainstem location in sporadic cerebral cavernous malformations (CCMs) provided new avenues for personalized treatment strategies, revealing distinct clinical presentations based on genetic alterations (ref: Planet doi.org/10.3171/2025.5.JNS25596/). Furthermore, LRRK2 deficiency was shown to mitigate amyloid β deposition in a murine model of Alzheimer's disease, indicating a potential protective role of this gene in neuroinflammation and disease progression (ref: Zhang doi.org/10.1038/s41398-025-03598-8/). The regulation of tau protein by circular RNA circCwc27 further elucidated shared pathogenic mechanisms between Alzheimer's disease and type 2 diabetes mellitus, emphasizing the interconnectedness of metabolic and neurodegenerative conditions (ref: Fang doi.org/10.1186/s40708-025-00277-8/). These findings collectively underscore the importance of genetic and epigenetic factors in understanding the complexities of neuropathology.

Research into neurodevelopmental disorders has provided valuable insights into the underlying pathological mechanisms. A study investigating the loss-of-function of Slc35a2 in oligodendrocytes demonstrated that this genetic alteration leads to hypomyelination and spontaneous seizures, replicating features observed in human malformations of cortical development (ref: Bartel doi.org/10.1111/epi.18697/). Additionally, the distinct reduction in microglial glucose uptake compared to astrocytes and neurons upon isolation from the brain environment highlighted the complexities of microglial energy metabolism, suggesting that in vitro studies may not fully capture in vivo dynamics (ref: Kunte doi.org/10.3389/fncel.2025.1572431/). The autonomy duration in patients with unresectable IDH wild-type glioblastomas was reported to be 7.7 months, indicating the need for further exploration of treatment strategies in this patient population (ref: Harlay doi.org/10.1007/s11060-025-05250-3/). Furthermore, the clinical outcomes and management of IDH-mutant astrocytomas were assessed, emphasizing the importance of molecular profiling in guiding treatment decisions (ref: Yuile doi.org/10.1093/nop/). Lastly, the investigation into gender role identity and its association with psychiatric symptoms provided new perspectives on the interplay between neurodevelopmental factors and mental health (ref: Rossi doi.org/10.3389/fpsyt.2025.1594762/).