Recent research has focused on the molecular mechanisms underlying various neuropathologies, particularly in high-grade gliomas and neurodegenerative diseases. A study demonstrated that avapritinib effectively targets PDGFRA-altered high-grade glioma, showing radiographic responses in 3 out of 7 cases, highlighting its potential therapeutic role (ref: Mayr doi.org/10.1016/j.ccell.2025.02.018/). Additionally, the role of microglia in neurodegenerative diseases has been elucidated through a long-read RNA sequencing atlas, which identified genetic regulation of splicing in microglia associated with various diseases (ref: Humphrey doi.org/10.1038/s41588-025-02099-0/). Furthermore, a study linking IL-1 and IL-6-related systemic inflammation in COVID-19 to microglial dysfunction and neurovascular inflammation suggests that these immune cells are central to the neurological manifestations observed in COVID-19 patients (ref: Fekete doi.org/10.1038/s41593-025-01871-z/). In Alzheimer's disease, interleukin-12 signaling has been shown to disrupt neuronal and oligodendrocyte homeostasis, indicating a critical role for neuroinflammation in disease progression (ref: Schneeberger doi.org/10.1038/s43587-025-00816-2/). Moreover, the co-pathology of alpha-synuclein has been associated with accelerated tau accumulation, emphasizing the need to consider this interaction in Alzheimer's research (ref: Franzmeier doi.org/10.1186/s13024-025-00822-3/).

Innovations in the diagnosis of brain tumors have emerged, focusing on rapid classification and the identification of biomarkers. A novel Bayesian framework, MethyLYZR, has been developed for the rapid classification of brain tumors from sparse epigenomic data, achieving results in under one hour, which is crucial for intraoperative decision-making (ref: Brändl doi.org/10.1038/s41591-024-03435-3/). Additionally, high-resolution proteomic analysis has revealed therapy-resistant subgroups in medulloblastoma, with MYC immunohistochemistry identified as a powerful prognostic marker for risk stratification (ref: Delaidelli doi.org/10.1093/neuonc/). The study of extracellular vesicles has also shown promise, with Tenascin-C serving as a clinical biomarker that enhances tumor-derived DNA analysis in glioblastoma patients, thereby improving monitoring of disease progression (ref: Salviano-Silva doi.org/10.1021/acsnano.4c13599/). Furthermore, strong nuclear expression of HOXB13 has been proposed as a reliable diagnostic marker for myxopapillary ependymoma, providing a new criterion for tumor classification (ref: Purkait doi.org/10.1007/s00401-025-02866-7/).

The interplay between neuroinflammation and neurodegeneration has been a focal point of recent studies, particularly in the context of Alzheimer's disease and COVID-19. Research has shown that microglial dysfunction and neurovascular inflammation are linked to systemic inflammation in COVID-19, suggesting that these immune responses may contribute to neurological abnormalities observed in affected patients (ref: Fekete doi.org/10.1038/s41593-025-01871-z/). In Alzheimer's disease, interleukin-12 signaling has been implicated in disrupting neuronal and oligodendrocyte homeostasis, indicating that neuroinflammatory pathways are critical to the disease's pathology (ref: Schneeberger doi.org/10.1038/s43587-025-00816-2/). Additionally, the co-pathology of alpha-synuclein has been associated with accelerated tau accumulation, underscoring the importance of considering multiple pathological factors in Alzheimer's research (ref: Franzmeier doi.org/10.1186/s13024-025-00822-3/). These findings collectively highlight the complex relationship between inflammation and neurodegeneration, suggesting that targeting inflammatory pathways may offer therapeutic potential.

Genetic and epigenetic factors play a crucial role in the development and progression of neuropathologies. A study utilizing long-read RNA sequencing has mapped genetic regulation of splicing in human microglia, revealing loci associated with neurodegenerative diseases (ref: Humphrey doi.org/10.1038/s41588-025-02099-0/). Furthermore, copy number variation analysis on chromosome 17q21.31 has identified associations with progressive supranuclear palsy, demonstrating that specific genetic alterations can increase disease risk (ref: Wang doi.org/10.1002/mds.30150/). The role of AMPK in glioblastoma adaptation to the tumor microenvironment has also been highlighted, suggesting that metabolic regulation is critical for tumor progression (ref: Lorenz doi.org/10.1186/s13046-025-03346-2/). Additionally, the study of C19orf66 has shown its potential in restricting Coxsackievirus B infection, indicating that host genetic factors can influence susceptibility to viral infections linked to neuropathologies (ref: Tan doi.org/10.1016/j.intimp.2025.114343/). These findings emphasize the importance of genetic and epigenetic research in understanding the mechanisms underlying neurological diseases.

The clinical implications of molecular pathology in brain tumors and neurodegenerative diseases are increasingly recognized, particularly in terms of prognosis and treatment strategies. High-resolution proteomic analysis of medulloblastoma has identified therapy-resistant subgroups, with MYC immunohistochemistry emerging as a significant prognostic marker for risk stratification (ref: Delaidelli doi.org/10.1093/neuonc/). In high-grade gliomas, targeting PDGFRA with avapritinib has shown promising results, indicating its potential as a therapeutic option for patients with specific genomic alterations (ref: Mayr doi.org/10.1016/j.ccell.2025.02.018/). The assessment of CDKN2A status in recurrent astrocytomas has also been highlighted as a critical factor for prognostication, emphasizing the need for standardized guidelines in interpreting genetic findings (ref: Jangir doi.org/10.1007/s10014-025-00496-1/). Furthermore, the study of α-synuclein seeding characteristics in frontotemporal dementia and multiple system atrophy has provided insights into the pathological similarities and differences between these conditions, which could inform future therapeutic approaches (ref: Cullinane doi.org/10.1111/nan.70013/).

The tumor microenvironment plays a pivotal role in therapy resistance, particularly in glioblastoma and other brain tumors. Research has demonstrated that PDGFRA alterations in high-grade glioma can be effectively targeted with avapritinib, which has shown radiographic responses in clinical cases, suggesting that understanding the tumor microenvironment can inform treatment strategies (ref: Mayr doi.org/10.1016/j.ccell.2025.02.018/). Additionally, a study on ARHGAP12 and ARHGAP29 has revealed their distinct regulatory effects on cell morphology and invasion, linking GSK-3 activity to cancer cell behavior and recurrence after treatment (ref: Cheng doi.org/10.1016/j.celrep.2025.115361/). The development of MethyLYZR, a framework for rapid brain tumor classification, highlights the importance of integrating epigenomic data to enhance diagnostic accuracy and treatment planning (ref: Brändl doi.org/10.1038/s41591-024-03435-3/). Moreover, longitudinal profiling of IDH-mutant astrocytomas has uncovered acquired mutations associated with inferior survival, emphasizing the need for continuous monitoring of tumor evolution in response to therapy (ref: Rodriguez Almaraz doi.org/10.1093/noajnl/).

Pathological insights into neurodegenerative diseases have revealed critical associations between genetic factors, inflammation, and disease progression. Research has shown that alpha-synuclein co-pathology is linked to accelerated tau accumulation in Alzheimer's disease, suggesting that this interaction may exacerbate neurodegeneration (ref: Franzmeier doi.org/10.1186/s13024-025-00822-3/). Additionally, DNA methylome and transcriptome profiles have been correlated with melanoma responses to anti-PD1 immunotherapy, indicating that epigenetic alterations can influence treatment outcomes (ref: Hossain doi.org/10.1016/j.canlet.2025.217638/). Furthermore, associations between early pregnancy telomere length and mitochondrial copy number with gestational diabetes mellitus and depressive symptoms have been identified, highlighting the potential impact of genetic and epigenetic factors on mental health (ref: Thirumoorthy doi.org/10.1016/j.psyneuen.2025.107431/). These findings underscore the complexity of neurodegenerative diseases and the need for a multifaceted approach to understanding their underlying mechanisms.