Recent studies have highlighted the complex roles of microglia in Alzheimer's disease (AD), particularly their spatial heterogeneity and functional states. Ardura-Fabregat et al. demonstrated that distinct microglial states exhibit varying chromatin accessibility and contribute differently to AD pathology, suggesting potential therapeutic targets (ref: Ardura-Fabregat doi.org/10.1038/s41593-025-02006-0/). Mrdjen et al. expanded on this by employing multiplexed ion beam imaging to reveal a spectrum of microglial proteomic profiles in human brains, emphasizing the limitations of rodent models in capturing human-specific microglial states (ref: Mrdjen doi.org/10.1038/s41590-025-02203-w/). Zhu et al. identified the G-protein-coupled receptor ADGRG1 as a driver of a protective microglial state through MYC activation, further elucidating the genetic underpinnings of microglial responses in AD (ref: Zhu doi.org/10.1016/j.neuron.2025.06.020/). D'Oliveira Albanus et al. explored the neuron-microglia cross-talk mediated by SEMA6D and TREM2, revealing that this interaction is crucial for microglial function and is disrupted in late AD stages (ref: D'Oliveira Albanus doi.org/10.1126/scitranslmed.adx0027/). Collectively, these studies underscore the importance of microglial dynamics and their potential as therapeutic targets in AD.

Genetic research has provided significant insights into the mechanisms underlying Alzheimer's disease (AD). Matatall et al. reported that TET2-mutant myeloid cells are associated with a 47% reduced risk of late-onset AD, highlighting the protective role of clonal hematopoiesis in AD progression (ref: Matatall doi.org/10.1016/j.stem.2025.06.006/). In a broader context, Rajabli et al. conducted a multi-ancestry genome-wide meta-analysis, identifying novel risk loci associated with AD, particularly in genes linked to neuronal development, which may inform future therapeutic strategies (ref: Rajabli doi.org/10.1186/s13059-025-03564-z/). Mrdjen et al. also contributed to this theme by mapping microglial states in human brains, reinforcing the need for human-specific models in genetic studies (ref: Mrdjen doi.org/10.1038/s41590-025-02203-w/). Furthermore, Shao et al. introduced a synthetic efferocytic receptor that enhances microglial clearance of amyloid-beta, showcasing a novel approach to modulating AD pathology (ref: Shao doi.org/10.1126/sciadv.ads6613/). These findings collectively emphasize the intricate genetic landscape of AD and the potential for targeted interventions.

Neuroinflammation plays a pivotal role in the pathogenesis of Alzheimer's disease (AD), with various studies elucidating its mechanisms and potential therapeutic targets. Hu et al. investigated the Chinese herbal formula Guilingji, revealing its potential to prevent AD through a network pharmacology approach, thus highlighting the importance of traditional medicine in modern therapeutic strategies (ref: Hu doi.org/10.1186/s13195-025-01790-y/). Brezani et al. examined the effects of ethanol consumption on amyloid pathology and neuroinflammation, demonstrating that ethanol exacerbates NLRP3 inflammasome activation in glial cells, which may contribute to AD progression (ref: Brezani doi.org/10.1186/s12974-025-03501-8/). Stephenson et al. focused on triglyceride metabolism, showing that lipid accumulation in microglia is linked to inflammatory responses, particularly in the context of the APOE4 genotype (ref: Stephenson doi.org/10.1016/j.celrep.2025.115961/). Giovannucci et al. utilized a human iPSC-derived triculture model to explore non-cell autonomous contributions to familial AD, providing insights into cell-cell interactions and potential therapeutic avenues (ref: Giovannucci doi.org/10.1016/j.tins.2025.07.010/). These studies collectively underscore the multifaceted nature of neuroinflammation in AD and the need for targeted interventions.

Innovative therapeutic strategies are being explored to combat Alzheimer's disease (AD), focusing on both pharmacological and non-pharmacological interventions. Zou et al. introduced a wearable ultrasonic device designed for continuous therapy aimed at amyloid-beta disaggregation, representing a novel approach to AD treatment (ref: Zou doi.org/10.1126/sciadv.adw1732/). Hu et al. highlighted the efficacy of the herbal formula Guilingji, suggesting its potential role in preventing AD through a network pharmacology framework (ref: Hu doi.org/10.1186/s13195-025-01790-y/). Zhang et al. investigated a synthetic peptide derived from scorpion venom, demonstrating its ability to improve cognitive dysfunction in APP/PS1 mice through modulation of microglial function (ref: Zhang doi.org/10.1111/bph.70124/). Zheng et al. reported that the combination of Tacrine and Rosmarinic Acid shows promise in enhancing therapeutic effects while reducing hepatotoxicity, indicating a potential avenue for safer AD treatments (ref: Zheng doi.org/10.1002/pca.70009/). These findings reflect a growing emphasis on diverse therapeutic modalities to address the complexities of AD.

The exploration of pathological features and biomarkers in Alzheimer's disease (AD) has advanced significantly, providing insights into disease mechanisms and potential diagnostic tools. Matatall et al. demonstrated that TET2-mutant myeloid cells can mitigate AD progression, suggesting a novel biomarker for risk assessment (ref: Matatall doi.org/10.1016/j.stem.2025.06.006/). Huang et al. investigated the interplay between Progranulin (PGRN) and soluble TREM2 (sTREM2), identifying their roles in modulating amyloid pathology, which may serve as biomarkers for disease progression (ref: Huang doi.org/10.1038/s41398-025-03457-6/). Saipuljumri et al. focused on the impact of palmitic acid on autolysosomal dysfunction, linking metabolic dysregulation to neuroinflammation and neurodegeneration, which could inform future biomarker development (ref: Saipuljumri doi.org/10.4103/NRR.NRR-D-25-00432/). Raghuvanshi et al. emphasized the importance of microglial phagocytosis in AD management, suggesting that targeting this process could yield new therapeutic strategies (ref: Raghuvanshi doi.org/10.2174/0118715273378092250623064748/). Collectively, these studies highlight the critical role of biomarkers in understanding AD pathology and guiding therapeutic interventions.

The crosstalk between neurodegenerative diseases is an emerging area of research, revealing shared mechanisms and potential therapeutic targets. Tuddenham et al. identified specific microglial subsets in amyotrophic lateral sclerosis (ALS), suggesting that targeting these cells could slow disease progression, thereby linking ALS and AD through shared immune mechanisms (ref: Tuddenham doi.org/10.1007/s00401-025-02913-3/). Zeng et al. explored the genetic associations between inflammatory bowel disease (IBD) and AD, finding that myeloid cell pathways may be common to both conditions, indicating a potential overlap in inflammatory mechanisms (ref: Zeng doi.org/10.1038/s41435-025-00344-4/). Chou et al. examined the immune microenvironment alterations following heat stroke, which may have implications for understanding neuroinflammation in both AD and other neurodegenerative diseases (ref: Chou doi.org/10.1016/j.compbiomed.2025.110773/). Bjørklund et al. discussed ozone-induced neurotoxicity, linking environmental factors to cognitive decline and neurodegenerative diseases, including AD and Parkinson's disease (ref: Bjørklund doi.org/10.2174/0109298673375058250624070823/). These studies underscore the interconnectedness of neurodegenerative diseases and the importance of a holistic approach to understanding their pathophysiology.

Environmental and lifestyle factors significantly influence the risk and progression of Alzheimer's disease (AD). Brezani et al. investigated the effects of ethanol consumption, revealing that it exacerbates amyloid pathology and neuroinflammation through NLRP3 inflammasome activation, highlighting the detrimental impact of alcohol on AD progression (ref: Brezani doi.org/10.1186/s12974-025-03501-8/). Hu et al. examined the Chinese herbal formula Guilingji, suggesting its potential to prevent AD, thus emphasizing the role of traditional remedies in mitigating disease onset (ref: Hu doi.org/10.1186/s13195-025-01790-y/). Zhang et al. discussed the therapeutic potential of N6-methyladenosine RNA methylation in neurodegenerative diseases, indicating that lifestyle factors affecting RNA metabolism could influence AD pathogenesis (ref: Zhang doi.org/10.4103/NRR.NRR-D-24-01648/). Bjørklund et al. also highlighted the neurotoxic effects of ozone exposure, linking environmental pollutants to cognitive decline and neurodegenerative diseases (ref: Bjørklund doi.org/10.2174/0109298673375058250624070823/). Collectively, these studies illustrate the complex interplay between environmental factors and AD, underscoring the need for preventive strategies.