Recent studies have highlighted the critical role of microglial activation in the pathogenesis of Alzheimer's disease (AD). One significant finding is the activation of the cGAS-STING pathway in microglia, which has been shown to contribute to AD pathology in 5xFAD mice, indicating that innate immune responses are pivotal in the disease's progression (ref: Xie doi.org/10.1038/s43587-022-00337-2/). Furthermore, the removal of neuronal APOE4, the strongest genetic risk factor for late-onset AD, significantly reduced tau pathology and neurodegeneration, suggesting that targeting APOE4 could mitigate microglial activation and its associated neuroinflammatory responses (ref: Koutsodendris doi.org/10.1038/s43587-023-00368-3/). Additionally, sleep deprivation has been shown to exacerbate microglial reactivity and amyloid-beta deposition, further linking lifestyle factors to microglial function in AD (ref: Parhizkar doi.org/10.1126/scitranslmed.ade6285/). Moreover, the role of microglial genes such as TREM2 and INPP5D has been explored, with findings indicating that mutations in these genes can restrict neuroprotective microglial responses, thereby exacerbating AD pathology (ref: Samuels doi.org/10.1002/alz.13089/; ref: Zhang doi.org/10.1111/cns.14219/). The therapeutic potential of modulating microglial activity through pharmacological agents or genetic interventions is emerging as a promising avenue for enhancing cognitive resilience and combating AD-related neurodegeneration.

Genetic factors play a crucial role in the susceptibility to Alzheimer's disease (AD), with several key variants identified that influence disease risk and progression. Notably, mutations in the TREM2 gene, particularly the R47H variant, have been associated with increased risk for late-onset AD, highlighting the importance of microglial function in neuroinflammation and amyloid pathology (ref: Jain doi.org/10.1186/s13024-023-00609-4/). Recent studies utilizing single-nucleus RNA sequencing have provided insights into the cellular effects of these genetic variants, revealing distinct transcriptional profiles in microglia and neurons from AD patients and risk variant carriers (ref: Brase doi.org/10.1038/s41467-023-37437-5/). Additionally, the heritability of late-onset AD has been quantified, with estimates ranging from 38% to 66%, emphasizing the significant genetic contribution to disease risk (ref: Baker doi.org/10.1371/journal.pone.0281440/). The APOE ε4 allele remains the most significant genetic risk factor, influencing neuroinflammation and amyloid deposition in cognitively unimpaired individuals (ref: Snellman doi.org/10.1186/s13195-023-01209-6/). Furthermore, the interplay between genetic variants and environmental factors, such as obesity and metabolic disorders, is increasingly recognized as a critical area for understanding AD pathogenesis and developing targeted interventions.

Neuroinflammation is a hallmark of Alzheimer's disease (AD), characterized by the activation of microglia and astrocytes in response to pathological changes in the brain. Recent research has demonstrated that the activation of hypothalamic-enhanced adult-born neurons can restore cognitive and affective functions in AD models, suggesting a potential therapeutic target for modulating neuroinflammation (ref: Li doi.org/10.1016/j.stem.2023.02.006/). Additionally, the regulation of TREM2 expression by transcription factor YY1 has been shown to protect against AD, indicating that enhancing TREM2 function could mitigate neuroinflammatory responses (ref: Lu doi.org/10.1016/j.jbc.2023.104688/). Moreover, the role of obesity-related circular RNAs in neurons and glia underlines the connection between metabolic disorders and neuroinflammation in AD (ref: Jo doi.org/10.3390/ijms24076235/). The development of an AAV-based model of tauopathy has further elucidated the role of microglia in tau pathology, emphasizing the need for targeted therapies that address both neuroinflammation and tau aggregation (ref: Duwat doi.org/10.1016/j.nbd.2023.106116/). Collectively, these findings underscore the complex interplay between neuroinflammation and immune responses in AD, highlighting potential avenues for therapeutic intervention.

The search for effective therapeutic approaches for Alzheimer's disease (AD) has led to innovative strategies aimed at targeting the underlying pathophysiology. One promising development is the erythrocyte membrane-coated nanotheranostic system designed for targeted immune regulation in AD, which has shown potential in ameliorating the disease's immune environment (ref: Su doi.org/10.1002/advs.202301361/). Additionally, the antioxidant punicalagin, derived from pomegranates, has been demonstrated to improve learning and memory deficits, redox homeostasis, and neuroinflammation in aging mice, suggesting its potential as a dietary intervention for AD (ref: Chen doi.org/10.1002/ptr.7848/). Furthermore, the association between APOE genotype and microglial morphology has been explored, revealing that the APOE ε4 allele influences microglial activation and may contribute to the neuroinflammatory processes observed in AD (ref: Kloske doi.org/10.1093/jnen/). The impact of sleep deprivation on microglial reactivity and amyloid-beta deposition further emphasizes the importance of lifestyle factors in therapeutic strategies (ref: Parhizkar doi.org/10.1126/scitranslmed.ade6285/). These findings collectively highlight the multifaceted nature of AD treatment, integrating pharmacological, dietary, and lifestyle interventions to address the complex pathology of the disease.

Microglial function is central to the pathophysiology of Alzheimer's disease (AD), with recent studies elucidating the cellular mechanisms underlying their activation and response to neurodegeneration. Research has shown that tau aggregates can enhance the rearrangement of podosomes in microglial cells, indicating a role for tau in modulating microglial behavior in the context of AD (ref: Chinnathambi doi.org/10.1016/j.bbamcr.2023.119477/). Additionally, the protective effects of carnosine on microglial cells under oxidative stress conditions have been demonstrated, suggesting that targeting metabolic pathways in microglia could offer therapeutic benefits (ref: Privitera doi.org/10.3389/fphar.2023.1161794/). Moreover, the influence of the APOE ε4 allele on neuroinflammation and amyloid pathology has been further characterized, revealing significant differences in microglial activation based on genetic background (ref: Snellman doi.org/10.1186/s13195-023-01209-6/). The regulation of TREM2 expression by YY1 has also been implicated in modulating microglial responses, highlighting the importance of transcriptional regulation in microglial function (ref: Lu doi.org/10.1016/j.jbc.2023.104688/). These insights into microglial mechanisms provide a foundation for developing targeted therapies aimed at enhancing microglial function and mitigating neurodegeneration in AD.

Environmental and lifestyle factors significantly influence the risk and progression of Alzheimer's disease (AD). Recent studies have demonstrated that exposure to quasi-ultrafine particulate matter accelerates memory impairment and AD-like neuropathology in mouse models, indicating that air pollution may exacerbate cognitive decline (ref: Kilian doi.org/10.1093/toxsci/). This highlights the need for public health interventions aimed at reducing exposure to environmental toxins as a potential strategy for mitigating AD risk. Additionally, the role of stem cell research in AD has gained attention, with bibliometric analyses revealing trends and hotspots in the field, suggesting that regenerative medicine may offer innovative therapeutic avenues (ref: Wang doi.org/10.1159/000528886/). The interplay between lifestyle factors, such as diet and physical activity, and genetic predispositions is increasingly recognized as critical in understanding AD pathogenesis and developing comprehensive prevention strategies. Collectively, these findings underscore the importance of considering environmental and lifestyle factors in the context of AD research and intervention.

The identification of reliable biomarkers for Alzheimer's disease (AD) is crucial for early diagnosis and monitoring disease progression. Recent research has highlighted the potential of microRNA expression in extracellular vesicles as a novel blood-based biomarker, with studies demonstrating that specific miRNAs can distinguish between mild cognitive impairment, AD, and cognitively normal individuals with high accuracy (ref: Kumar doi.org/10.1002/alz.13055/). This advancement in biomarker discovery could facilitate earlier interventions and personalized treatment strategies. Additionally, the influence of the APOE ε4 allele on neuroinflammation and amyloid pathology has been explored through imaging and blood biomarker assessments, revealing significant differences in biomarker profiles among genetically at-risk individuals (ref: Snellman doi.org/10.1186/s13195-023-01209-6/). The development of animal models, such as AAV-based tauopathy models, has also provided insights into the cellular mechanisms underlying AD, further supporting the need for biomarkers that reflect both genetic and pathological changes (ref: Duwat doi.org/10.1016/j.nbd.2023.106116/). These findings collectively emphasize the importance of integrating biomarker research into clinical practice to enhance the diagnosis and management of AD.