Microglia play a crucial role in the pathogenesis of Alzheimer's disease (AD), acting as the brain's resident immune cells. Recent studies have highlighted the complex interplay between microglial activation and amyloid-beta (Aβ) pathology. For instance, the APOE-Christchurch variant has been shown to suppress microglial cGAS-STING responses, enhancing the clearance of pathological tau aggregates in mouse models of AD (ref: Akay doi.org/10.1016/j.immuni.2025.07.019/). In contrast, Aβ exposure leads to the upregulation of Glypican 4 (GPC4) in microglia, exacerbating neuronal tau pathology and toxicity (ref: Holmes doi.org/10.1186/s13024-025-00883-4/). Furthermore, deficiencies in MS4A6A/Ms4a6d disrupt neuroprotective microglial functions and promote inflammation, indicating that genetic factors significantly influence microglial responses in AD (ref: Jiao doi.org/10.1186/s13024-025-00887-0/). The transcriptional landscape of human microglia in AD reveals dysregulation of gene expression associated with various disease phenotypes, highlighting the importance of microglial gene-gene coordination and coexpression modules (ref: Kosoy doi.org/10.1038/s41593-025-02020-2/). Additionally, early intervention with anti-Aβ immunotherapy has shown promise in attenuating microglial activation without inducing exhaustion, suggesting that timely therapeutic strategies could modulate microglial behavior favorably (ref: de Weerd doi.org/10.1186/s13024-025-00878-1/). Overall, these findings underscore the dual role of microglia in both promoting and mitigating AD pathology, emphasizing the need for targeted therapeutic approaches that consider microglial dynamics.

Amyloid-beta (Aβ) pathology is a central feature of Alzheimer's disease, and recent research has elucidated various mechanisms by which it influences neuroinflammation. Midkine (MDK), an understudied protein, has been found to attenuate Aβ fibril assembly and plaque formation, suggesting a protective role against amyloid pathology (ref: Zaman doi.org/10.1038/s41594-025-01657-8/). Conversely, chronic exposure to PM2.5 has been shown to exacerbate Aβ deposition and tau hyperphosphorylation, indicating that environmental factors can significantly influence AD pathology (ref: Wei doi.org/10.1016/j.ecoenv.2025.118918/). Moreover, the effects of low-intensity pulsed ultrasound (LIPUS) have been investigated, revealing its potential to enhance microglial-mediated Aβ clearance and preserve synaptic integrity, thus improving cognitive function in AD models (ref: Su doi.org/10.1016/j.expneurol.2025.115420/). In addition to these findings, the role of alcohol consumption in accelerating tau pathology and modifying microglial responses has been highlighted, suggesting that lifestyle factors can exacerbate neuroinflammatory processes in AD (ref: Maphis doi.org/10.1111/acer.70123/). The therapeutic potential of targeting neuroinflammation through Formyl Peptide Receptor 2 (FPR2) agonists has also been explored, indicating a promising avenue for intervention in neuroinflammatory diseases (ref: Francavilla doi.org/10.1021/acschemneuro.5c00308/). Collectively, these studies underscore the intricate relationship between amyloid pathology and neuroinflammation, emphasizing the need for multifaceted therapeutic strategies that address both aspects.

The genetic landscape of Alzheimer's disease (AD) is complex, with recent studies revealing critical insights into the molecular mechanisms underlying the disease. The histone demethylase PHF2 has been identified as a key regulator of inflammatory genes in AD, with significant upregulation observed in postmortem human tissues and AD mouse models (ref: Yang doi.org/10.1038/s41380-025-03181-z/). Additionally, the APOE4 allele has been shown to reprogram microglial lipid metabolism, leading to energy deficits and impaired phagocytic capacity, which exacerbates neuroinflammation and amyloid clearance (ref: Chen doi.org/10.5582/bst.2025.01148/). This highlights the importance of genetic factors in modulating microglial function and the overall pathophysiology of AD. Furthermore, the development of a novel empirical Bayesian framework, gruyere, allows for improved mapping of rare genetic variants associated with AD, enhancing our understanding of the genotype-phenotype relationship (ref: Das doi.org/10.1016/j.ajhg.2025.07.016/). The transcriptional landscape of human microglia has also been characterized, revealing distinct gene expression patterns associated with various AD phenotypes, which may inform future therapeutic strategies (ref: Kosoy doi.org/10.1038/s41593-025-02020-2/). Overall, these findings underscore the critical role of genetic and molecular mechanisms in shaping the pathogenesis of AD and highlight potential targets for intervention.

Recent advancements in therapeutic strategies for Alzheimer's disease (AD) have focused on innovative approaches to enhance cognitive function and reduce neuroinflammation. One promising avenue involves the use of human iPSC-derived mononuclear phagocytes, which have demonstrated the ability to improve cognition and neural health in multiple mouse models of aging and AD (ref: Moser doi.org/10.1002/advs.202417848/). This approach capitalizes on the regenerative potential of stem cells to combat age-related cognitive decline. Additionally, the therapeutic potential of a gadolinium chelate complex conjugated with vanillic acid has been evaluated, showing promise as a contrast agent that targets activated microglia in AD models (ref: Jeon doi.org/10.1021/acsptsci.5c00316/). Moreover, the Chuanxiong-Renshen medicine pair has been shown to ameliorate neuroinflammation in AD through modulation of the PKC-α/NF-κB signaling pathway, suggesting that traditional medicine may offer valuable insights into AD treatment (ref: Wang doi.org/10.1016/j.phymed.2025.157161/). The identification of flavonoid compounds with neuroprotective effects also highlights the potential of natural products in AD therapy, with systematic screening revealing several candidates that could penetrate the blood-brain barrier (ref: Ding doi.org/10.1142/S0192415X25500806/). Collectively, these studies emphasize the importance of exploring diverse therapeutic strategies to address the multifaceted challenges posed by AD.

Environmental and lifestyle factors play a significant role in the development and progression of Alzheimer's disease (AD). Recent findings indicate that chronic exposure to PM2.5 exacerbates AD pathology through lysosomal dysfunction, leading to increased cognitive impairment and enhanced Aβ plaque deposition in mouse models (ref: Wei doi.org/10.1016/j.ecoenv.2025.118918/). This underscores the impact of environmental pollutants on neurodegenerative processes. Additionally, excessive alcohol consumption has been identified as a modifiable risk factor for AD, with studies showing that it accelerates gait impairments and modifies tau aggregation in mouse models (ref: Maphis doi.org/10.1111/acer.70123/). Furthermore, the influence of musical rhythm exposure on AD progression has been explored, suggesting that rhythmic auditory stimulation may enhance cognitive functions and potentially delay disease onset (ref: Li doi.org/10.1016/j.isci.2025.113168/). These findings highlight the importance of lifestyle interventions, such as reducing environmental toxins and promoting cognitive engagement through music, in mitigating the risk of AD. Overall, understanding the interplay between environmental factors and lifestyle choices is crucial for developing effective prevention strategies against AD.

Circadian rhythms have emerged as a significant factor in the pathophysiology of Alzheimer's disease (AD), with disruptions in these rhythms potentially contributing to neurodegeneration. Recent research utilizing single-nucleus RNA sequencing has revealed that while core clock rhythms are preserved in AD, many cell-type-specific circadian outputs are disrupted, indicating a complex relationship between circadian biology and AD pathology (ref: Hollis doi.org/10.1016/j.neuron.2025.07.010/). This disruption may influence neuroinflammatory processes and cognitive decline, suggesting that circadian modulation could be a potential therapeutic target. Additionally, early intervention with anti-Aβ immunotherapy has been shown to attenuate microglial activation and improve amyloid plaque pathology, further emphasizing the importance of timing in therapeutic strategies (ref: de Weerd doi.org/10.1186/s13024-025-00878-1/). The interplay between circadian rhythms and neuroinflammation highlights the need for further investigation into how circadian disruptions may exacerbate neurodegenerative processes and how restoring rhythmicity could benefit AD patients.

Neuroinflammation is a hallmark of Alzheimer's disease (AD), and recent studies have focused on understanding the immune response and its implications for disease progression. The development of a non-parametric meta-analysis method, SumRank, has improved the reproducibility of differentially expressed genes (DEGs) in single-cell transcriptomic studies, revealing insights into the immune landscape of AD (ref: Nakatsuka doi.org/10.1038/s41467-025-62579-z/). This method has highlighted the importance of specific immune-related genes in distinguishing AD from other neurodegenerative diseases, thereby enhancing our understanding of the immune response in AD. Furthermore, leveraging functional annotations to map rare genetic variants associated with AD has provided new insights into the genetic underpinnings of neuroinflammation (ref: Das doi.org/10.1016/j.ajhg.2025.07.016/). The identification of programmed cell death signatures driving microglial transformation in AD underscores the dynamic nature of the immune response and its potential role in disease pathology (ref: Li doi.org/10.3389/fimmu.2025.1610717/). Collectively, these findings emphasize the need for targeted therapeutic strategies that modulate the immune response to mitigate neuroinflammation in AD.

Cellular senescence is increasingly recognized as a critical factor in the aging process and the development of Alzheimer's disease (AD). Recent studies have demonstrated that dysregulated cholesterol metabolism in microglia contributes to cellular senescence in AD, highlighting the importance of metabolic pathways in neurodegenerative processes (ref: Li doi.org/10.1111/acel.70189/). This finding suggests that targeting metabolic dysregulation could be a potential therapeutic strategy to mitigate the effects of senescence in AD. Additionally, the anti-inflammatory effects of beta-hydroxybutyrate (BHB) on microglial cells have been investigated, revealing that BHB elicits concentration-dependent effects that may contribute to memory and longevity benefits in the context of a ketogenic diet (ref: Garcia doi.org/10.3389/fragi.2025.1628835/). These insights into the relationship between cellular senescence, metabolism, and neuroinflammation underscore the need for further research into how aging-related processes influence AD pathology and how interventions targeting these pathways could improve outcomes for patients.