Microglial activation plays a crucial role in the neuroinflammatory processes associated with Alzheimer's disease (AD). Recent studies have highlighted the significance of the PLCG2 gene in modulating inflammatory responses in microglia. For instance, Tsai et al. demonstrated that PLCG2 expression is induced by amyloid plaques in a 5xFAD mouse model, suggesting its involvement in the inflammatory response linked to AD pathology (ref: Tsai doi.org/10.1186/s13073-022-01022-0/). Additionally, Claes et al. explored the protective P522R variant of PLCG2, which enhances antigen presentation in microglia, indicating a potential therapeutic target for reducing AD risk (ref: Claes doi.org/10.1002/alz.12577/). The NLRP3 inflammasome has also emerged as a pivotal player in neuroinflammation, with Stancu et al. showing that NLRP3 deficiency in tauP301S transgenic mice leads to reduced tau pathology and hippocampal atrophy, underscoring its role in neurodegeneration (ref: Stancu doi.org/10.1002/glia.24160/). Zhang et al. further emphasized the therapeutic potential of targeting NLRP3 signaling to mitigate microglial inflammation, presenting a promising avenue for AD treatment (ref: Zhang doi.org/10.1016/j.bmc.2022.116645/). Overall, these findings collectively highlight the multifaceted role of microglial activation and neuroinflammation in AD, suggesting that targeting these pathways could yield significant therapeutic benefits.

The genetic and molecular underpinnings of Alzheimer's disease (AD) have been elucidated through various studies integrating genomics and transcriptomics. Rosenthal et al. conducted a comprehensive analysis that identified a network of 142 risk genes associated with AD, many of which are linked to synaptic functions, thereby providing insights into the molecular interactions that contribute to AD pathology (ref: Rosenthal doi.org/10.1371/journal.pcbi.1009903/). Additionally, Hu et al. highlighted the role of endocannabinoid signaling in astrocytes, demonstrating that enhancing this pathway can promote recovery from traumatic brain injury, a known risk factor for AD (ref: Hu doi.org/10.1093/brain/). The regulation of acetylcholinesterase during inflammatory responses in microglial cells was also investigated by Xia et al., who proposed that acetylcholine plays a non-classical role in modulating immune responses, further linking cholinergic signaling to neuroinflammation in AD (ref: Xia doi.org/10.1096/fj.202101302RR/). These studies collectively underscore the intricate genetic and molecular mechanisms that contribute to AD, emphasizing the need for targeted therapeutic strategies.

Therapeutic strategies targeting microglial function have gained traction in the context of Alzheimer's disease (AD). Owlett et al. explored the effects of Gas6 overexpression in the APP/PS1 model, finding that while it reduced plaque burden, it paradoxically worsened behavioral outcomes in a sex-dependent manner, highlighting the complexity of microglial modulation (ref: Owlett doi.org/10.1186/s12974-022-02397-y/). In a different approach, Rudnitskaya et al. investigated the effects of a mitochondria-targeted antioxidant, SkQ1, on glial support during AD-like pathology, revealing that it could correct deficits in neurogenesis and astrocyte density, thus offering a potential therapeutic avenue (ref: Rudnitskaya doi.org/10.3390/ijms23031134/). Furthermore, the modulation of microglial activation states through Neuregulin-1 was shown by Ma et al. to influence the balance between pro-inflammatory and anti-inflammatory responses, suggesting that targeting microglial phenotype conversion could be beneficial in AD treatment (ref: Ma doi.org/10.1007/s11033-022-07249-9/). These findings collectively illustrate the potential of various therapeutic approaches aimed at modulating microglial function to ameliorate AD pathology.

Environmental and lifestyle factors significantly influence the progression and pathology of Alzheimer's disease (AD). Tian et al. demonstrated that exposure to sevoflurane exacerbates AD progression through the NLRP3/caspase-1 pathway, indicating that anesthetic exposure may have detrimental effects on neurodegeneration (ref: Tian doi.org/10.3389/fcell.2021.801422/). In contrast, Liu et al. reported that exosomes derived from bone-marrow mesenchymal stem cells can alleviate cognitive decline in AD-like mice by improving BDNF-related neuropathology, suggesting that certain lifestyle interventions may have protective effects (ref: Liu doi.org/10.1186/s12974-022-02393-2/). Furthermore, Hu et al. highlighted the role of traumatic brain injury as a significant risk factor for developing AD, emphasizing the need for preventive measures in at-risk populations (ref: Hu doi.org/10.1093/brain/). These studies collectively underscore the importance of understanding how environmental and lifestyle factors can modulate AD risk and progression, paving the way for potential preventive strategies.

Sex differences in Alzheimer's disease (AD) pathology have garnered increasing attention, with studies indicating that these differences may influence disease progression and response to treatment. Lecordier et al. investigated the impact of multifocal cerebral microinfarcts on early AD pathology, revealing that these lesions affect pathology progression in a sex-dependent manner, with implications for understanding how male and female brains respond differently to AD-related changes (ref: Lecordier doi.org/10.3389/fimmu.2021.813536/). Mela et al. further explored sex-specific effects of DMF on microglial activation, highlighting the need to consider sex as a biological variable in neurodegenerative disease research (ref: Mela doi.org/10.3390/cells11040729/). Additionally, Rudnitskaya et al. noted that changes in glial support during AD-like pathology differ between sexes, suggesting that therapeutic interventions may need to be tailored based on sex to enhance efficacy (ref: Rudnitskaya doi.org/10.3390/ijms23031134/). Collectively, these findings emphasize the importance of incorporating sex differences into AD research and treatment strategies.

Astrocytes play a pivotal role in the pathophysiology of Alzheimer's disease (AD), particularly in relation to amyloid-beta accumulation and neuroinflammation. Mahan et al. demonstrated that selective reduction of astrocyte apoE isoforms significantly decreases Aβ accumulation and plaque-related pathology in a mouse model of amyloidosis, highlighting the critical role of astrocytic apoE in AD (ref: Mahan doi.org/10.1186/s13024-022-00516-0/). In a related study, Owlett et al. found that Gas6 overexpression in astrocytes reduced plaque burden but negatively impacted behavior in a sex-dependent manner, indicating the complexity of astrocytic roles in AD pathology (ref: Owlett doi.org/10.1186/s12974-022-02397-y/). Furthermore, Rudnitskaya et al. investigated the changes in glial support during the development of AD-like pathology, revealing that astrocyte density decreases in the early stages of the disease, which may contribute to neurodegeneration (ref: Rudnitskaya doi.org/10.3390/ijms23031134/). These studies collectively underscore the multifaceted roles of astrocytes in AD, suggesting that targeting astrocytic functions may offer new therapeutic avenues.

Inflammatory pathways are central to the neurodegenerative processes observed in Alzheimer's disease (AD). The NLRP3 inflammasome has been identified as a key player in mediating neuroinflammation, with Stancu et al. demonstrating that NLRP3 deficiency in tauP301S mice leads to reduced tau pathology and neurodegeneration, suggesting its potential as a therapeutic target (ref: Stancu doi.org/10.1002/glia.24160/). Additionally, Tian et al. reported that sevoflurane exacerbates AD progression through the NLRP3/caspase-1 pathway, indicating that anesthetic exposure may trigger inflammatory responses that worsen neurodegeneration (ref: Tian doi.org/10.3389/fcell.2021.801422/). Zhang et al. further emphasized the importance of targeting NLRP3 signaling to inhibit microglial inflammation, presenting a promising strategy for mitigating neuroinflammatory responses in AD (ref: Zhang doi.org/10.1016/j.bmc.2022.116645/). Collectively, these findings highlight the critical role of inflammatory pathways in AD pathology and the potential for therapeutic interventions aimed at modulating these pathways.