The molecular mechanisms underlying Alzheimer's disease (AD) have garnered significant attention, particularly focusing on the amyloid-β (Aβ) pathway, which is central to AD pathophysiology. Hampel et al. systematically reviewed the literature surrounding the Aβ cycle, emphasizing its role in synaptic failure and neurodegeneration. They highlighted that Aβ dyshomeostasis is a critical factor in the disease's progression, suggesting that targeting this pathway could lead to effective disease-modifying therapies (ref: Hampel doi.org/10.1038/s41380-021-01249-0/). Additionally, Watanabe et al. explored the transcriptional downregulation of FAM3C in AD brains, linking reduced levels of transcription factors SP1 and EBF1 to this downregulation, thereby providing insights into the molecular alterations occurring in AD (ref: Watanabe doi.org/10.1093/hmg/). Furthermore, the study by Dávila-Bouziguet et al. introduced a model of non-demented individuals with AD neuropathology, which raises questions about the mechanisms that confer cognitive resilience despite the presence of typical AD pathologies (ref: Dávila-Bouziguet doi.org/10.1093/brain/). Collectively, these studies underscore the complexity of AD's molecular landscape and the potential for novel therapeutic strategies targeting specific pathways.

Neuroinflammation plays a pivotal role in neurodegenerative diseases, as evidenced by a systematic review conducted by Loan et al., which quantified molecular markers of inflammation in brain tissue following intracerebral hemorrhage (ICH). Their meta-analysis revealed significant inflammatory responses, suggesting that targeting these pathways could offer therapeutic benefits (ref: Loan doi.org/10.1136/jnnp-2021-327098/). In a related study, Ho et al. demonstrated that TDP-43, a protein associated with amyotrophic lateral sclerosis and frontotemporal dementia, influences cholesterol metabolism in oligodendrocytes, linking neuroinflammation to metabolic dysregulation in the central nervous system (ref: Ho doi.org/10.1083/jcb.201910213/). Additionally, Hsiao et al. investigated telomere length shortening in microglia, suggesting that accelerated senescence may contribute to neurocognitive deficits in HIV-infected individuals, further emphasizing the intersection of inflammation and neurodegeneration (ref: Hsiao doi.org/10.3390/vaccines9070721/). These findings collectively highlight the multifaceted role of neuroinflammation in various neurological disorders and its potential as a therapeutic target.

Recent advancements in tumor biology have illuminated the molecular underpinnings of various brain tumors. Alhalabi et al. identified PATZ1 fusions as a novel molecularly distinct entity among neuroepithelial tumors, emphasizing the importance of DNA methylation profiling in tumor classification (ref: Alhalabi doi.org/10.1007/s00401-021-02354-8/). Similarly, Sievers et al. reported on recurrent fusions in PLAGL1 that define a distinct subset of pediatric-type supratentorial neuroepithelial tumors, underscoring the heterogeneity of CNS tumors and the need for precise molecular characterization (ref: Sievers doi.org/10.1007/s00401-021-02356-6/). Coltin et al. examined subgroup-specific outcomes in adult medulloblastoma, revealing that chromosome 8 loss is associated with improved survival, a finding that contrasts with pediatric cases where different genetic alterations dominate (ref: Coltin doi.org/10.1007/s00401-021-02358-4/). These studies collectively illustrate the evolving landscape of tumor biology, where molecular profiling is essential for accurate diagnosis and tailored treatment strategies.

The role of genetic and epigenetic factors in neurological disorders has been increasingly recognized, particularly in the context of cancer. Bauer et al. explored the epigenetic landscape of platinum-resistant epithelial ovarian cancer, identifying specific enhancer changes that could serve as biomarkers for patient stratification (ref: Bauer doi.org/10.3390/cancers13153801/). Steinbügl et al. provided clinical evidence for the efficacy of decitabine, an epigenetically active agent, in treating relapsed rhabdoid tumors, highlighting the potential of epigenetic therapies in pediatric oncology (ref: Steinbügl doi.org/10.1002/pbc.29267/). Furthermore, Altmann et al. conducted a systems-level analysis revealing that microglial activation significantly influences cortical thickness in common epilepsies, suggesting that genetic predispositions may interact with inflammatory processes in disease manifestation (ref: Altmann doi.org/10.1111/nan.12758/). Together, these studies emphasize the intricate interplay between genetic, epigenetic, and environmental factors in shaping neurological disorders.

Cognitive function and neuroprotection are critical areas of research, particularly in the context of aging and neurodegenerative diseases. Islam et al. identified irisin, an exercise-induced hormone, as a key regulator of cognitive function, demonstrating that its absence impairs cognitive abilities in models of aging and Alzheimer's disease (ref: Islam doi.org/10.1038/s42255-021-00438-z/). This finding underscores the potential of exercise and its molecular mediators in promoting cognitive health. Cousins et al. examined longitudinal changes in naming and repetition in patients with primary progressive aphasia, linking these changes to AD pathology and suggesting that cognitive decline is closely tied to underlying neurodegenerative processes (ref: Cousins doi.org/10.1002/trc2.12188/). Additionally, Buerke et al. explored age-related risk factors for suicidal behavior in depression, revealing that neurocognitive performance remains a significant risk factor across the lifespan (ref: Buerke doi.org/10.1016/j.jad.2021.08.014/). Collectively, these studies highlight the importance of understanding cognitive dynamics and protective factors in the context of neurological health.

Molecular imaging and biomarkers are pivotal in advancing our understanding of neurological disorders. Nuessle et al. investigated the diagnostic performance of apparent diffusion coefficient (ADC) values in stratifying molecular glioma subtypes, demonstrating significant differences across glioma grades, which could enhance diagnostic accuracy (ref: Nuessle doi.org/10.3390/jcm10163451/). In a review by Güntekin et al., the authors discussed event-related EEG oscillations in Alzheimer's disease, identifying consistent abnormalities that could serve as biomarkers for cognitive deficits associated with various dementias (ref: Güntekin doi.org/10.1111/psyp.13934/). Hanke et al. focused on actionable molecular drivers in lung cancer patients with brain metastases, emphasizing the need for tailored therapeutic approaches based on molecular profiling (ref: Hanke doi.org/10.1016/j.clineuro.2021.106841/). These studies collectively illustrate the critical role of molecular imaging and biomarkers in diagnosing and managing neurological disorders.

Neurodevelopmental and pediatric neuropathology has gained attention with the establishment of registries and studies focusing on molecular alterations in pediatric cancers. The INFORM registry, as reported by van Tilburg et al., has provided valuable insights into clinical outcomes for pediatric patients with high-evidence molecular targets, emphasizing the importance of personalized medicine in this demographic (ref: van Tilburg doi.org/10.1158/2159-8290.CD-21-0094/). Dávila-Bouziguet et al. introduced a model of non-demented individuals with Alzheimer's disease neuropathology, highlighting the need for further research into protective mechanisms that allow for cognitive preservation despite the presence of typical pathologies (ref: Dávila-Bouziguet doi.org/10.1093/brain/). Additionally, Alhalabi et al. and Coltin et al. contributed to the understanding of pediatric-type tumors, reinforcing the necessity for molecular profiling in improving outcomes for young patients (ref: Alhalabi doi.org/10.1007/s00401-021-02354-8/; ref: Coltin doi.org/10.1007/s00401-021-02358-4/). These findings underscore the significance of early detection and intervention in pediatric neuropathology.

The impact of COVID-19 on neurological health has become a critical area of research, with studies exploring the neuropathological consequences of SARS-CoV-2 infection. Maiese et al. conducted a systematic review of neuropathological findings in COVID-19 patients, revealing significant insights into the virus's effects on the central nervous system (ref: Maiese doi.org/10.1111/bpa.13013/). Cosentino et al. critically reviewed the literature, arguing against direct brain invasion by SARS-CoV-2, while emphasizing the need for further investigation into the mechanisms underlying neurological symptoms associated with the virus (ref: Cosentino doi.org/10.1111/ene.15045/). Additionally, Apra et al. provided a molecular description of meningeal solitary fibrous tumors, contributing to the understanding of tumor pathology in the context of COVID-19 (ref: Apra doi.org/10.1007/s11060-021-03830-7/). These studies collectively highlight the urgent need to understand the neurological implications of COVID-19 and the potential long-term effects on brain health.