Microglial activation plays a pivotal role in the neuroinflammatory processes associated with Alzheimer's disease (AD). Recent studies have highlighted the significance of BIN1, a protein that regulates microglial activation. Sudwarts et al. demonstrated that silencing BIN1 in primary microglial cultures led to increased proinflammatory responses, indicating its crucial role in modulating microglial behavior (ref: Sudwarts doi.org/10.1186/s13024-022-00535-x/). Additionally, Zhao et al. explored the metabolic pathways of microglia, revealing that activated microglia switch from oxidative phosphorylation to glycolysis, a change that may influence their inflammatory responses in AD (ref: Zhao doi.org/10.1186/s13024-022-00541-z/). Furthermore, Kenkhuis et al. reported that iron accumulation in microglia induces oxidative stress and alters inflammatory polarization, suggesting a complex interplay between iron metabolism and neuroinflammation in AD (ref: Kenkhuis doi.org/10.1016/j.stemcr.2022.04.006/). These findings underscore the multifaceted nature of microglial activation and its implications for AD pathology. The role of peripheral immune cells in AD has also been investigated, with Yan et al. revealing that monocyte-derived cells contribute to the microglial population surrounding amyloid plaques, although their effectiveness in plaque clearance remains limited (ref: Yan doi.org/10.1172/JCI152565/). This highlights the potential for targeting both resident and peripheral immune cells in therapeutic strategies. Moreover, the TREM2 R47H variant, associated with increased AD risk, has been shown to affect microglial function and may link neuroinflammation to musculoskeletal alterations, as reported by Essex et al. (ref: Essex doi.org/10.1002/jbmr.4572/). Overall, these studies illustrate the critical involvement of microglial activation and neuroinflammation in the progression of Alzheimer's disease, suggesting that therapeutic interventions aimed at modulating these processes could be beneficial.

Metabolic alterations in microglia are increasingly recognized as key factors in the pathogenesis of Alzheimer's disease (AD). Zhao et al. provided insights into the metabolic switch that occurs in activated microglia, where they transition from oxidative phosphorylation to glycolysis, a change that may enhance their inflammatory response (ref: Zhao doi.org/10.1186/s13024-022-00541-z/). This metabolic reprogramming is critical for understanding how microglial activation contributes to neuroinflammation and cognitive decline in AD. Furthermore, the study by Yan et al. on peripheral monocyte-derived cells highlighted the contribution of these cells to the microglial population in the context of amyloid plaque pathogenesis, suggesting that metabolic changes in these cells may also play a role in disease progression (ref: Yan doi.org/10.1172/JCI152565/). In addition to metabolic shifts, environmental factors such as air pollution have been implicated in altering microglial function. Patten et al. found that traffic-related air pollution affects cytokine levels in the hippocampus of AD model rats, indicating that external factors can influence microglial activity and potentially exacerbate neuroinflammation (ref: Patten doi.org/10.3389/fncel.2022.861733/). This interplay between metabolic changes and environmental influences underscores the complexity of microglial responses in AD. Moreover, the systematic review by Mittal et al. synthesized various mechanisms contributing to AD, emphasizing the role of oxidative stress and metabolic dysregulation in the disease's etiology (ref: Mittal doi.org/10.2174/1871527321666220510144127/). Collectively, these findings highlight the importance of understanding metabolic changes in microglia as potential therapeutic targets in Alzheimer's disease.

The interaction between microglia and amyloid pathology is a central theme in Alzheimer's disease research. Yan et al. demonstrated that microglia, while surrounding amyloid plaques, are ineffective in clearing them, which contributes to disease progression (ref: Yan doi.org/10.1172/JCI152565/). This study utilized a genetic fate-mapping approach to reveal that peripheral monocyte-derived cells contribute to the microglial population associated with amyloid plaques, indicating a complex relationship between different immune cell types in the brain (ref: Yan doi.org/10.1172/JCI152565/). Furthermore, Li et al. explored the neuroprotective effects of exosomes derived from M2 microglia, showing that these exosomes can attenuate neuronal impairment and mitochondrial dysfunction in AD models, suggesting a potential therapeutic avenue for enhancing microglial function against amyloid toxicity (ref: Li doi.org/10.3389/fncel.2022.874102/). In addition to these findings, Qin et al. investigated the therapeutic potential of artesunate, which restored mitochondrial dynamics and alleviated neuronal injury in AD models, further emphasizing the importance of mitochondrial health in the context of amyloid pathology (ref: Qin doi.org/10.1111/jnc.15620/). The studies collectively highlight the dual role of microglia in both supporting neuronal health and contributing to amyloid pathology, suggesting that strategies aimed at modulating microglial activity could be crucial in developing effective therapies for Alzheimer's disease.

Therapeutic strategies targeting microglia in Alzheimer's disease (AD) are gaining traction as researchers seek to modulate neuroinflammation and improve cognitive outcomes. Ye et al. introduced oxytocin-loaded nanogels designed to inhibit innate inflammatory responses in microglia, presenting a novel approach for early intervention in AD (ref: Ye doi.org/10.1021/acsami.2c00007/). This innovative delivery system aims to mitigate chronic neuroinflammation, which is a hallmark of AD pathology. Additionally, Cao et al. evaluated derivatives of sarcodonin A, which were found to reverse M1 polarization in microglia through the MAPK/NF-κB pathway, suggesting that natural compounds may offer therapeutic benefits by restoring microglial balance (ref: Cao doi.org/10.1016/j.bioorg.2022.105854/). Moreover, Qin et al. explored the effects of artesunate, a derivative of artemisinin, on AD models, demonstrating its ability to restore mitochondrial dynamics and alleviate neuronal injury (ref: Qin doi.org/10.1111/jnc.15620/). These findings underscore the potential of targeting microglial metabolism and function as a therapeutic strategy. The interplay between microglial activation and environmental factors, as highlighted by Patten et al., further emphasizes the need for comprehensive approaches that consider both intrinsic and extrinsic influences on microglial behavior (ref: Patten doi.org/10.3389/fncel.2022.861733/). Collectively, these studies illustrate the promising landscape of therapeutic interventions aimed at modulating microglial activity to combat Alzheimer's disease.

Genetic and molecular factors significantly influence microglial function in Alzheimer's disease (AD). The TREM2 R47H variant, identified as a risk factor for AD, has been shown to affect microglial behavior and is linked to musculoskeletal alterations in mice, as reported by Essex et al. (ref: Essex doi.org/10.1002/jbmr.4572/). This variant underscores the importance of genetic predispositions in shaping microglial responses and their role in neuroinflammation. Additionally, Kenkhuis et al. investigated the effects of iron accumulation on human iPSC-derived microglia, revealing that iron treatment increased ferritin levels and altered inflammatory polarization, suggesting that genetic factors may interact with environmental influences to exacerbate AD pathology (ref: Kenkhuis doi.org/10.1016/j.stemcr.2022.04.006/). Moreover, Liu et al. identified the Platelet Activating Factor Receptor as a potential biomarker and therapeutic target for AD, emphasizing the need for early diagnosis and intervention strategies (ref: Liu doi.org/10.3389/fnagi.2022.856628/). Bioinformatics analyses conducted by Belonwu et al. further elucidated the molecular pathways involved in AD, particularly focusing on the role of apolipoprotein E4 (APOE4) in microglial function (ref: Belonwu doi.org/10.3389/fnagi.2022.749991/). These findings collectively highlight the intricate interplay between genetic factors and microglial function, suggesting that targeted therapies could be developed to modulate microglial activity based on individual genetic profiles.

Environmental and lifestyle factors play a crucial role in the development and progression of Alzheimer's disease (AD). Patten et al. demonstrated that traffic-related air pollution significantly alters cytokine levels in the hippocampus of AD model rats, indicating that environmental pollutants can exacerbate neuroinflammation and potentially accelerate cognitive decline (ref: Patten doi.org/10.3389/fncel.2022.861733/). This study highlights the importance of understanding how external factors can influence microglial activity and overall brain health. Additionally, Soriano et al. explored the impact of fecal microbiota transplantation from AD mice on brain trauma outcomes in wild-type controls, revealing that alterations in gut microbiota can affect neuroinflammation and cognitive function (ref: Soriano doi.org/10.3390/ijms23094476/). Moreover, Cao et al. investigated the effects of transcranial electromagnetic treatment on cytokine levels in AD patients, finding that this intervention could rebalance inflammatory markers and improve cognitive function (ref: Cao doi.org/10.3389/fnagi.2022.829049/). These findings underscore the potential for lifestyle interventions and environmental modifications to influence the trajectory of AD. The interplay between environmental factors and neuroinflammation emphasizes the need for comprehensive approaches that consider both genetic predispositions and external influences in the management of Alzheimer's disease.

Neuroinflammation is increasingly recognized as a key contributor to cognitive decline in Alzheimer's disease (AD). Giridharan et al. examined the effects of sepsis on cognitive function, hypothesizing that inflammation disrupts the microbiota-gut-brain axis, leading to impairments in memory and executive functioning (ref: Giridharan doi.org/10.1186/s12974-022-02472-4/). This study highlights the broader implications of systemic inflammation on brain health and cognitive performance. Additionally, Schütze et al. emphasized the association between bacterial infections and cognitive decline in AD patients, suggesting that acute infections may exacerbate neurodegenerative processes (ref: Schütze doi.org/10.3233/ADR-210049/). Furthermore, Zhang et al. explored the activation of reactive astrocytes by β-amyloid, revealing that Aβ oligomers can enhance glycolysis in astrocytes, which may contribute to neuroinflammation and cognitive deficits (ref: Zhang doi.org/10.1007/s11033-022-07319-y/). The paradoxical relationship between cerebrospinal fluid sTREM2 levels and brain structural damage rates in AD, as reported by Leng et al., further illustrates the complex dynamics of neuroinflammation and its impact on cognitive decline (ref: Leng doi.org/10.3233/JAD-220102/). Collectively, these studies underscore the critical role of neuroinflammation in cognitive decline, suggesting that targeting inflammatory pathways may offer therapeutic potential in Alzheimer's disease.