Recent studies have highlighted the critical role of genetic and epigenetic mechanisms in various neuropathological conditions, particularly gliomas. Dejaegher et al. demonstrated that DNA methylation-based subclassification of glioblastomas (GBM) correlates with T-cell infiltration and patient survival, suggesting that epigenetic profiles can inform therapeutic strategies (ref: Dejaegher doi.org/10.1093/neuonc/). Similarly, Sievers et al. identified a distinct DNA methylation profile in a subset of pediatric thalamic gliomas, which is associated with alterations in the epidermal growth factor receptor (EGFR), indicating a unique biological behavior in these tumors (ref: Sievers doi.org/10.1093/neuonc/). Furthermore, Suwala et al. reported a novel group of IDH-mutant astrocytomas characterized by mismatch repair deficiency, which is linked to poor prognosis, underscoring the importance of genetic alterations in treatment resistance (ref: Suwala doi.org/10.1007/s00401-020-02243-6/). In a broader context, Feng et al. constructed a radiosensitivity prediction signature based on genomic methylation, which could enhance clinical decision-making for GBM patients undergoing radiotherapy (ref: Feng doi.org/10.1038/s41598-020-77259-9/). These findings collectively emphasize the potential of integrating genetic and epigenetic data to improve patient stratification and treatment outcomes in gliomas and other brain tumors.

The tumor microenvironment, particularly the interactions between tumor cells and immune components, plays a pivotal role in tumor progression and response to therapy. Tan et al. demonstrated that inhibiting CSF1R leads to the depletion of tumor-associated macrophages (TAMs) in a mouse model of sonic hedgehog medulloblastoma, resulting in reduced tumor progression (ref: Tan doi.org/10.1038/s41388-020-01536-0/). This finding highlights the importance of TAMs in promoting tumor growth and suggests that targeting these cells could be a viable therapeutic strategy. In a different context, Zhai et al. utilized single-cell RNA sequencing to explore the dynamic interactions between glioma stem cells and immune cells during tumorigenesis, revealing shifts in immune cell populations that may influence tumor behavior (ref: Zhai doi.org/10.3389/fimmu.2020.581209/). Additionally, Broekaart et al. investigated the role of matrix metalloproteinases in neuroinflammation and seizure activity, suggesting that targeting these pathways may mitigate tumor-related seizures and improve cognitive outcomes (ref: Broekaart doi.org/10.1172/JCI138332/). Collectively, these studies underscore the complexity of the tumor microenvironment and the necessity of understanding immune interactions to develop effective therapies.

Neurodegenerative disorders such as Alzheimer's disease (AD) and frontotemporal dementia (FTD) are characterized by complex pathophysiological mechanisms, and recent research has focused on identifying biomarkers for early diagnosis and understanding disease progression. Dewan et al. found pathogenic huntingtin repeat expansions in a small subset of FTD and amyotrophic lateral sclerosis (ALS) patients, suggesting a potential genetic overlap between these disorders (ref: Dewan doi.org/10.1016/j.neuron.2020.11.005/). In another study, Soleimani-Meigooni et al. compared 18F-flortaucipir PET imaging with post-mortem pathology, revealing that tau pathology is more pronounced in AD compared to other tauopathies, which could aid in differential diagnosis (ref: Soleimani-Meigooni doi.org/10.1093/brain/). Furthermore, Calvo-Flores Guzmán et al. discussed the interplay between beta-amyloid and tau in AD, emphasizing the role of neuroinflammation and synaptic dysfunction in disease progression (ref: Calvo-Flores Guzmán doi.org/10.3389/fnmol.2020.552073/). These findings highlight the importance of integrating genetic, imaging, and biochemical data to enhance our understanding of neurodegenerative diseases and improve diagnostic accuracy.

Molecular imaging techniques have emerged as powerful tools for diagnosing and understanding neurological disorders. Lesman-Segev et al. conducted a study comparing the diagnostic accuracy of PIB and FDG PET imaging, demonstrating that PIB PET is more effective in identifying Alzheimer's disease pathology compared to FDG PET, which can show patterns associated with other neurodegenerative conditions (ref: Lesman-Segev doi.org/10.1002/ana.25968/). This highlights the necessity of selecting appropriate imaging modalities based on the clinical context. Additionally, Bohnert et al. explored the application of metabolomics in postmortem cerebrospinal fluid diagnostics, revealing that metabolite profiling can provide insights into central nervous system-related pathological processes (ref: Bohnert doi.org/10.1007/s00414-020-02462-2/). Furthermore, Laimer et al. utilized hyperspectral imaging to differentiate between amalgam tattoos and other pigmented lesions, showcasing the potential of advanced imaging techniques in clinical diagnostics (ref: Laimer doi.org/10.1002/jbio.202000424/). These studies collectively underscore the transformative impact of molecular imaging and diagnostic techniques in enhancing our understanding and management of neurological disorders.

The neuropathological features associated with infectious and inflammatory conditions have gained significant attention, particularly in the context of COVID-19. Kirschenbaum et al. reported that patients with COVID-19 exhibited intracerebral endotheliitis and microbleeds, suggesting that the virus can have direct effects on the central nervous system, which may contribute to neurological symptoms observed in infected individuals (ref: Kirschenbaum doi.org/10.1111/nan.12677/). This finding emphasizes the need for further investigation into the neurological sequelae of COVID-19. In another study, Sriram et al. examined the biological effects of inhaled hydraulic fracturing sand dust, revealing neuroinflammation and altered synaptic protein expression, which raises concerns about occupational exposure and its potential long-term effects on brain health (ref: Sriram doi.org/10.1016/j.taap.2020.115300/). Additionally, Minasi et al. explored alternative lengthening of telomeres in pediatric high-grade gliomas, indicating that telomere maintenance mechanisms may play a role in tumor biology and response to therapy (ref: Minasi doi.org/10.1007/s00381-020-04933-8/). These studies highlight the intricate relationship between infectious processes, inflammation, and neuropathological changes.

The identification of therapeutic targets and understanding drug resistance mechanisms in brain tumors are critical for improving treatment outcomes. Karschnia et al. investigated the extent of MGMT promoter methylation in gliomas, finding that higher levels of methylation correlate with favorable outcomes, particularly in IDH-mutant astrocytomas (ref: Karschnia doi.org/10.1038/s41598-020-76312-x/). This suggests that MGMT methylation status could serve as a valuable biomarker for predicting treatment response. Additionally, Feng et al. developed a novel methylation signature that predicts radiotherapy sensitivity in glioma patients, indicating its potential utility in clinical practice (ref: Feng doi.org/10.1038/s41598-020-77259-9/). Furthermore, Peláez Coyotl et al. explored the effects of an antimicrobial peptide on cellular respiration in tumor cells, highlighting the potential for novel therapeutic strategies targeting metabolic pathways (ref: Peláez Coyotl doi.org/10.3390/pharmaceutics12111071/). These findings collectively underscore the importance of understanding molecular mechanisms in developing effective therapies and overcoming drug resistance in brain tumors.

Cognitive and behavioral aspects of neuropathology are increasingly recognized as critical components in understanding various neurological disorders. Ji et al. found that cortisol-dehydroepiandrosterone (DHEA) ratios are inversely associated with hippocampal and prefrontal brain volume in individuals with schizophrenia, suggesting that hormonal imbalances may contribute to cognitive deficits observed in this population (ref: Ji doi.org/10.1016/j.psyneuen.2020.104916/). This highlights the need for further exploration of endocrine factors in cognitive health. Additionally, Russell et al. examined social cognition impairments in familial frontotemporal dementia, revealing early deficits in emotion processing and theory of mind abilities, which could serve as early indicators of disease progression (ref: Russell doi.org/10.1016/j.cortex.2020.08.023/). Moreover, Rizk et al. compared characteristics of depressed suicide attempters with and without substance use disorders, finding that those with a history of substance use had more lethal attempts, emphasizing the need for targeted prevention strategies (ref: Rizk doi.org/10.1016/j.jpsychires.2020.10.041/). These studies collectively underscore the importance of integrating cognitive and behavioral assessments into the clinical management of neurological disorders.