Research on Alzheimer's disease (AD) has focused on various genetic and molecular factors influencing its pathology. A significant study developed a knock-in model allowing for the inducible switching between the risk allele APOE4 and the protective allele APOE2. This model demonstrated that switching to APOE2 resulted in improved metabolic signatures, reduced neuropathology, and enhanced cognitive function, highlighting the potential of genetic modulation in AD therapy (ref: Golden doi.org/10.1038/s41593-025-02094-y/). Another study explored the role of the PS1-ELK1 protein-protein interaction, revealing that targeting this interaction with a peptide-based inhibitor reduced Aβ production and alleviated memory decline, suggesting a novel therapeutic avenue (ref: Yi doi.org/10.1016/j.ijbiomac.2025.149074/). Furthermore, proteomic profiling in rapidly progressive Alzheimer's disease identified mitochondrial dysregulation and the role of DLDH in amyloid beta aggregation, emphasizing the complexity of AD subtypes and their distinct molecular mechanisms (ref: Zafar doi.org/10.1007/s12035-025-05327-0/). In addition, the therapeutic potential of the HAEEPGP peptide against β-amyloid-induced neuropathology was investigated, demonstrating its ability to suppress amyloidogenesis in vivo, which could address the limitations of current monoclonal antibody therapies (ref: Kechko doi.org/10.1007/s12035-025-05349-8/). Overall, these studies underscore the multifaceted nature of AD and the importance of targeting various molecular pathways for effective treatment strategies.

The molecular landscape of brain tumors, particularly infant-type hemispheric glioma (IHG) and spinal ependymomas, has been elucidated through systematic studies. A meta-analysis of 164 patients with IHG revealed that these tumors are predominantly non-metastatic and diagnosed at a median age of 3.4 months, emphasizing the need for tailored treatment strategies for this rare condition (ref: Chavaz doi.org/10.1093/neuonc/). In spinal ependymomas, single-nucleus transcriptomics identified intratumoral heterogeneity, distinguishing subtypes with varying prognoses, which could guide clinical management (ref: Hack doi.org/10.1093/neuonc/). Additionally, a framework utilizing DNA methylation profiling was proposed to predict outcomes and responses to radiotherapy in meningioma patients, facilitating the integration of molecular models into clinical practice (ref: Landry doi.org/10.1093/neuonc/). The clinical and molecular characterization of pediatric cavernous malformations further highlighted the genetic underpinnings and natural history of these lesions, providing insights into their management (ref: Benichi doi.org/10.1093/braincomms/). Lastly, establishing an optimal qMSP cutoff for MGMT promoter methylation in glioblastoma has significant implications for prognostic stratification, enhancing the clinical decision-making process (ref: Huseyinoglu doi.org/10.1186/s12885-025-15225-2/). Collectively, these findings illustrate the critical role of molecular diagnostics in improving treatment outcomes for brain tumors.

Neuroinflammation plays a pivotal role in various neurological disorders, with recent studies uncovering mechanisms linking immune responses to disease progression. One study demonstrated that neutrophil extracellular traps (NETs) and peptidylarginine deiminase 4 (PAD4) activation contribute to diabetic cardiomyopathy and kidney disease, highlighting the intersection of metabolic and cardiovascular pathology (ref: Schommer doi.org/10.1093/eurheartj/). Another investigation into spinal cord injury revealed that astrocytic CCL7 exacerbates neuropathology by recruiting microglia, suggesting that targeting this chemokine could mitigate inflammatory damage (ref: Song doi.org/10.1096/fj.202500902R/). The potential of Bruton Tyrosine Kinase (BTK) inhibition to limit inflammation in multiple sclerosis was also explored, showing that BTK inhibitors can promote regulatory B cells while suppressing proinflammatory responses, indicating a promising therapeutic strategy (ref: Dybowski doi.org/10.1212/NXI.0000000000200510/). Additionally, research on alcohol-induced neuroimmune dysregulation revealed that chronic alcohol exposure leads to significant inflammatory signaling alterations among neurons, astrocytes, and microglia, which may contribute to cognitive impairments (ref: Boreland doi.org/10.1016/j.alcohol.2025.10.006/). These studies collectively emphasize the importance of understanding neuroinflammatory mechanisms to develop targeted therapies for neurodegenerative and inflammatory diseases.

Recent advancements in understanding neurodegeneration have highlighted the genetic and molecular factors contributing to diseases such as Parkinson's and chronic traumatic encephalopathy (CTE). The G2019S LRRK2 mutation was shown to exacerbate α-synuclein and tau neuropathology through distinct pathways, suggesting that different protein aggregates may interact differently with neuroinflammatory processes (ref: Tsafaras doi.org/10.1007/s00401-025-02956-6/). Another study investigated the role of TMEM106B genetic variation in modulating microglial activation and cytokine responses in CTE, revealing that the risk genotype is associated with increased disease severity and TDP-43 inclusions, underscoring the genetic influence on neuroinflammatory responses (ref: Hartman doi.org/10.1007/s00401-025-02955-7/). Furthermore, research on p.A53T-α-synuclein astrocytes demonstrated that dysregulated proteostasis aggravates Lewy-like neuropathology in a Parkinson's disease model, indicating the critical role of astrocytic health in neurodegenerative processes (ref: Paschou doi.org/10.1073/pnas.2505240122/). The use of single-nucleus multiome analysis in amyotrophic lateral sclerosis (ALS) provided insights into motor neuron vulnerability and the role of non-motor neuron cells, further elucidating the complex cellular interactions in neurodegeneration (ref: Takeuchi doi.org/10.1093/brain/). These findings collectively enhance our understanding of the genetic and molecular underpinnings of neurodegenerative diseases, paving the way for targeted therapeutic interventions.

The impact of environmental factors on neurodevelopmental disorders has been a focal point of recent research, particularly regarding the effects of nutritional deficiencies and toxic exposures. A study on guinea pigs demonstrated that time-limited vitamin C deprivation leads to significant neurodevelopmental changes, suggesting that vitamin C plays a crucial role in maintaining brain structure and function (ref: Čapo doi.org/10.3390/nu17213484/). Additionally, lead exposure during development was shown to alter synaptic organization and protein expression in the rat hippocampus, correlating with increased anxiety-like behavior, thereby emphasizing the neurotoxic effects of environmental pollutants (ref: Shirke doi.org/10.1016/j.jhazmat.2025.140582/). Furthermore, the molecular characterization of oxaliplatin-induced peripheral neurotoxicity revealed a complex spectrum of painful manifestations, highlighting the need for understanding the mechanisms underlying chemotherapy-induced neurotoxicity (ref: Pozzi doi.org/10.1111/jns.70078/). These studies underscore the importance of addressing environmental factors in the context of neurodevelopmental disorders, as they can significantly influence neurological outcomes.

Innovative therapeutic strategies are being explored to address various neuropathological conditions, with a focus on enhancing immune responses and targeting specific molecular pathways. A study on natural killer (NK) cells demonstrated that a chimeric antigen receptor enhances their functions and anti-tumor activity, suggesting a promising approach for cancer immunotherapy (ref: Pan doi.org/10.7150/thno.120909/). In the context of Alzheimer's disease, the HAEEPGP peptide was shown to suppress β-amyloid-induced neuropathology, providing a potential alternative to traditional monoclonal antibody therapies that face challenges with blood-brain barrier permeability (ref: Kechko doi.org/10.1007/s12035-025-05349-8/). Additionally, proteomic analysis of brain samples from individuals with Down syndrome revealed Alzheimer-like phenotypes, which could inform therapeutic strategies for this population as they age (ref: Di Domenico doi.org/10.1007/s12035-025-05432-0/). The molecular characterization of oxaliplatin-induced peripheral neurotoxicity also highlighted the need for targeted interventions to manage chemotherapy-related pain (ref: Pozzi doi.org/10.1111/jns.70078/). These findings collectively illustrate the ongoing efforts to develop effective therapeutic strategies for various neuropathological conditions, emphasizing the importance of personalized medicine.

Research into cerebral and spinal vascular malformations has provided insights into their clinical and molecular characteristics, particularly in pediatric populations. A comprehensive study analyzed 257 patients with cavernous malformations, revealing a significant mutational burden that correlates with radiological features and hemorrhagic risk, thereby enhancing the understanding of these lesions' natural history (ref: Benichi doi.org/10.1093/braincomms/). Furthermore, the molecular characterization of oxaliplatin-induced peripheral neurotoxicity highlighted the complex spectrum of painful manifestations associated with chemotherapy, which may intersect with vascular malformations (ref: Pozzi doi.org/10.1111/jns.70078/). Additionally, neurodevelopmental changes due to vitamin C deprivation in guinea pigs suggest potential links between nutritional deficiencies and vascular malformations, warranting further investigation into their interrelationship (ref: Čapo doi.org/10.3390/nu17213484/). These studies underscore the importance of understanding the genetic and environmental factors influencing vascular malformations to improve clinical outcomes and therapeutic approaches.

The development of neurobiomarkers and diagnostic innovations is crucial for advancing the understanding and management of neurological diseases. A prospective study demonstrated the utility of hair root and CSF samples in diagnosing human prion disease using the RT-QuIC assay, achieving a specificity of 100% and sensitivity of 45.8%, indicating the potential for noninvasive diagnostic methods (ref: Dong doi.org/10.1038/s41598-025-25310-y/). Additionally, discussions at the Society of Toxicologic Pathology symposium highlighted the importance of novel biomarkers in detecting nervous system changes in preclinical studies, which can enhance drug efficacy evaluations and monitor neurological diseases (ref: Sadekova doi.org/10.1177/01926233251394637/). The application of spatial technologies in neuro-omics was also emphasized, showcasing their potential in understanding genetic and molecular expression profiles in both human diseases and nonclinical models (ref: Bangari doi.org/10.1177/01926233251391184/). These advancements in neurobiomarkers and diagnostic innovations are paving the way for improved detection, monitoring, and treatment strategies for various neurological conditions.