The interplay between neuroinflammation and neurodegeneration is further elucidated by Mason et al., who found that microglia can slow tauopathy progression by regulating the spread of phosphorylated tau in both the central nervous system and blood (ref: Mason doi.org/10.1038/s41590-025-02198-4/). This highlights the dual role of the immune response in neurodegenerative diseases, where it can either exacerbate or mitigate disease progression. Additionally, the study by Janelidze et al. on plasma biomarkers in individuals with Down syndrome suggests that biomarkers like p-tau217 and GFAP could serve as valuable tools for monitoring Alzheimer's disease progression, emphasizing the importance of early detection and intervention (ref: Janelidze doi.org/10.1016/S1474-4422(25)00158-9/). Collectively, these studies underscore the multifaceted mechanisms underlying neurodegeneration, pointing to potential biomarkers and therapeutic strategies that could be leveraged for intervention.

Moreover, Zhang et al. identified a novel role for YAP in regulating TDP-43 condensates, which are implicated in amyotrophic lateral sclerosis (ALS). Their findings suggest that YAP's interaction with TDP-43 is crucial for maintaining the dynamics of these condensates, potentially offering new therapeutic targets for ALS (ref: Zhang doi.org/10.1038/s41556-025-01685-y/). Additionally, the study by Gather et al. on the lincRNA Pantr1 elucidated its role as a target gene of FOXG1, which is involved in neurodevelopmental disorders, thereby linking transcriptional regulation to neurodegenerative processes (ref: Gather doi.org/10.1093/nar/). Together, these studies highlight the critical genetic and molecular factors that contribute to neurodegeneration, paving the way for future research aimed at therapeutic interventions.

In the context of Parkinson's disease, Orrú et al. assessed the diagnostic and prognostic value of α-synuclein seed amplification assay kinetic measures, revealing that baseline measures could predict cognitive decline, thus highlighting the potential of these biomarkers in clinical settings (ref: Orrú doi.org/10.1016/S1474-4422(25)00157-7/). Furthermore, Moscoso et al. provided estimates of tau PET positivity and its association with clinical outcomes, finding that an Aβ PET-positive/tau PET-positive profile significantly increased the risk of progression to dementia (ref: Moscoso doi.org/10.1001/jama.2025.7817/). These findings collectively underscore the critical role of biomarkers in understanding cognitive decline and facilitating timely therapeutic interventions.

In a related context, Castellani et al. reported on myeloid-mediated cerebral amyloid vasculitis, which underscores the potential role of the immune response in brain atrophy following anti-Aβ therapy (ref: Castellani doi.org/10.1172/JCI195137/). This finding raises important questions about the implications of immune modulation in the treatment of neurodegenerative diseases. Additionally, the study by Gather et al. on the lincRNA Pantr1 and its interaction with FOXG1 suggests that transcriptional regulation may also play a role in modulating immune responses in neurodevelopmental disorders (ref: Gather doi.org/10.1093/nar/). Together, these studies emphasize the complex interplay between neuroinflammation and neurodegeneration, highlighting the need for further research to explore therapeutic avenues that could leverage the immune response.

Moreover, Moscoso et al. provided insights into the frequency of tau PET positivity and its association with clinical outcomes, revealing that a tau PET-positive profile significantly correlates with an increased risk of progression to dementia (ref: Moscoso doi.org/10.1001/jama.2025.7817/). This finding emphasizes the critical role of tau imaging in understanding disease progression and tailoring therapeutic strategies. Additionally, the study by Orrú et al. on α-synuclein seed amplification assay kinetic measures further illustrates the potential of combining neuroimaging with biomarker assessments to enhance diagnostic precision in Parkinson's disease (ref: Orrú doi.org/10.1016/S1474-4422(25)00157-7/). Collectively, these studies highlight the transformative impact of neuroimaging and biomarker integration in the early detection and monitoring of neurodegenerative diseases.

In addition, da Rocha et al. investigated the protective effects of exercise in an Alzheimer's disease mouse model, revealing that exercise induces distinct transcriptomic responses in the dentate gyrus, particularly in immature neurons (ref: da Rocha doi.org/10.1038/s41593-025-01971-w/). This finding suggests that lifestyle interventions, such as physical activity, may play a crucial role in mitigating neurodegenerative processes. Furthermore, Mason et al. highlighted the potential of harnessing immune responses to slow tauopathy progression, indicating that immunomodulatory strategies could be beneficial in treating neurodegenerative diseases (ref: Mason doi.org/10.1038/s41590-025-02198-4/). Together, these studies illustrate the diverse therapeutic avenues being explored to combat neurodegenerative diseases, emphasizing the need for continued innovation in treatment strategies.

Additionally, Wen et al. utilized artificial intelligence to identify dimensional neuroimaging endophenotypes (DNEs) that capture neuroanatomical patterns associated with various brain disorders, including Alzheimer's disease and schizophrenia (ref: Wen doi.org/10.1038/s41551-025-01412-w/). This innovative approach may help elucidate the underlying mechanisms of disease progression and the influence of environmental factors on brain health. Furthermore, Jiang et al. developed a novel photoacoustic imaging technique to investigate mobile Cu(II) dynamics, which could provide insights into the role of metal ions in neurodegenerative processes (ref: Jiang doi.org/10.1002/anie.202500149/). Collectively, these studies highlight the importance of considering environmental and lifestyle factors in the context of neurodegenerative diseases, paving the way for future research in this area.

In addition, the study by Ramachandran et al. on metachromatic leukodystrophy demonstrated the efficacy of AAV-mediated ARSA replacement in mice, revealing significant reductions in toxic sulfatides and associated pathology (ref: Ramachandran doi.org/10.1172/JCI185001/). This research emphasizes the importance of addressing cellular changes and metabolic dysfunctions in neurodegenerative disorders. Furthermore, the investigation of genetic modifiers of somatic expansion in Huntington's disease by an unnamed author sheds light on the complex interplay between genetic factors and clinical phenotypes, suggesting that somatic expansion is driven by a mismatch repair-related process (ref: doi.org/10.1038/s41588-025-02191-5/). Together, these studies provide valuable insights into the pathological features and cellular changes that characterize neurodegenerative diseases, informing future therapeutic approaches.