Recent studies have highlighted the critical role of microglia in the pathogenesis of Alzheimer's disease (AD), particularly focusing on their function in neuroinflammation. Mendiola et al. established a multiomic profiling approach to elucidate how blood proteins influence microglial polarization and neurotoxicity, revealing that blood-induced innate immune polarization significantly affects microglial behavior (ref: Mendiola doi.org/10.1038/s41590-023-01522-0/). In a related study, Li et al. conducted a systematic review and meta-analysis, demonstrating that lipocalin-2 levels are significantly elevated in AD patients, suggesting its potential as a biomarker for the disease (ref: Li doi.org/10.1016/j.arr.2023.101984/). Furthermore, Bieger et al. discussed neuroinflammation biomarkers within the AT(N) framework, emphasizing the importance of inflammatory changes in response to amyloid-beta and tau accumulation, which are pivotal in AD progression (ref: Bieger doi.org/10.14283/jpad.2023.54/). These findings collectively underscore the multifaceted role of microglia in neuroinflammation and their potential as therapeutic targets in AD. In addition to these insights, several studies explored the therapeutic implications of modulating microglial activity. Ospondpant et al. demonstrated that extracts from Dracaena cochinchinensis significantly suppress inflammatory responses in activated microglial cells, indicating a promising avenue for anti-neuroinflammatory therapies (ref: Ospondpant doi.org/10.1016/j.phymed.2023.154936/). Yang et al. introduced a reactive oxygen species-responsive nanoscavenger designed to promote mitophagy, which may enhance neuronal health and mitigate neuroinflammation in AD (ref: Yang doi.org/10.1002/smll.202302284/). These studies highlight the potential for targeting microglial functions and neuroinflammatory pathways as a therapeutic strategy in AD.

The exploration of molecular mechanisms and biomarkers in Alzheimer's disease (AD) has gained momentum, particularly with the identification of genetic factors and their implications in disease progression. Bouzid et al. investigated the association between clonal hematopoiesis and AD, revealing that mutations in hematopoietic stem cells may confer a protective effect against the disease, suggesting a complex interplay between the immune system and neurodegeneration (ref: Bouzid doi.org/10.1038/s41591-023-02397-2/). This finding aligns with the work of Fominykh et al., who identified shared genetic loci between AD and multiple sclerosis, highlighting the role of neuroinflammation in both conditions and suggesting potential therapeutic targets (ref: Fominykh doi.org/10.1016/j.nbd.2023.106174/). Moreover, the role of tau pathology in AD has been further elucidated by Mate De Gerando et al., who demonstrated that both fibrillar and oligomeric tau contribute to tau seeding and spreading in vivo, challenging the traditional view of tau as solely a toxic aggregate (ref: Mate De Gerando doi.org/10.1007/s00401-023-02600-1/). Ennerfelt et al. also contributed to this discourse by showing that CARD9 modulates microglial responses and attenuates amyloid-beta pathology, reinforcing the significance of innate immune receptors in AD (ref: Ennerfelt doi.org/10.1073/pnas.2303760120/). Collectively, these studies underscore the intricate molecular landscape of AD, revealing potential biomarkers and therapeutic targets that could pave the way for novel interventions.

Therapeutic strategies for Alzheimer's disease (AD) are increasingly focusing on innovative approaches that target underlying pathophysiological mechanisms. Yang et al. introduced a novel reactive oxygen species-responsive nanoscavenger aimed at promoting mitophagy, which may enhance neuronal health and offer a targeted treatment for AD (ref: Yang doi.org/10.1002/smll.202302284/). This approach highlights the potential of nanotechnology in addressing mitochondrial dysfunction, a key feature in AD pathology. In a different vein, Feng et al. demonstrated that high-intensity interval training (HIIT) can ameliorate AD-like pathology by regulating astrocyte phenotype and AQP4 polarization, suggesting that lifestyle interventions may have significant neuroprotective effects (ref: Feng doi.org/10.7150/thno.81951/). Additionally, the anti-inflammatory properties of telmisartan were explored by Fu et al., who found that it alleviates AD-related neuropathologies and cognitive impairments, indicating that existing medications may be repurposed for AD treatment (ref: Fu doi.org/10.3233/JAD-230133/). The extracts of Dracaena cochinchinensis were also shown to suppress inflammatory responses in activated microglial cells, further supporting the potential for natural products in therapeutic applications (ref: Ospondpant doi.org/10.1016/j.phymed.2023.154936/). These findings collectively emphasize the importance of both pharmacological and non-pharmacological interventions in the management of AD, paving the way for more comprehensive treatment strategies.

The interplay between genetic and environmental factors in Alzheimer's disease (AD) is a critical area of research, with recent studies shedding light on shared genetic loci and their implications for disease susceptibility. Fominykh et al. identified 16 shared genetic loci between AD and multiple sclerosis, suggesting that immune-linked genetic variants may play a significant role in both neurodegenerative and inflammatory pathways (ref: Fominykh doi.org/10.1016/j.nbd.2023.106174/). This discovery opens avenues for further exploration of genetic predispositions that may influence the development of AD, particularly in the context of neuroinflammation. Moreover, Sideris-Lampretsas et al. examined the role of galectin-3 in modulating inflammatory nociception in wild-type and AD model mice, revealing that chronic pain mechanisms may differ significantly in AD, which could have implications for treatment strategies (ref: Sideris-Lampretsas doi.org/10.1038/s41467-023-39077-1/). Additionally, Hines et al. investigated the pathological aging of canines, finding parallels with human AD, which may provide insights into the environmental and biological factors influencing cognitive decline (ref: Hines doi.org/10.3389/fnagi.2023.1128521/). These studies collectively highlight the complex genetic and environmental interactions that contribute to AD, emphasizing the need for a multifaceted approach in understanding and addressing the disease.

Neurodegeneration and cognitive decline in Alzheimer's disease (AD) are closely linked to neuroinflammatory processes and metabolic dysfunction. Gao et al. demonstrated that tetrahydroxy stilbene glycoside ameliorates neuroinflammation in AD through the cGAS-STING pathway, highlighting the potential of targeting inflammatory mechanisms to improve cognitive outcomes (ref: Gao doi.org/10.1016/j.ejphar.2023.175809/). This study underscores the importance of understanding the inflammatory landscape in AD and its impact on cognitive function. In a complementary study, Jiang et al. utilized RNA sequencing to analyze differential gene expression in aging and AD models, revealing that cognitive function declines significantly in 3xTg AD mice compared to age-matched controls (ref: Jiang doi.org/10.3233/JAD-230292/). Furthermore, Alidoust et al. explored the therapeutic potential of stem cell-conditioned medium, suggesting that it may offer a promising treatment avenue for AD-related cognitive impairments (ref: Alidoust doi.org/10.1016/j.bbr.2023.114543/). These findings collectively emphasize the critical relationship between neuroinflammation, cognitive decline, and potential therapeutic interventions in AD.

The activation and metabolic changes of microglia are pivotal in the context of Alzheimer's disease (AD), influencing both neuroinflammation and neurodegeneration. Schlotterose et al. highlighted that resveratrol mitigates metabolic dysregulation in human microglia, suggesting that dietary interventions may modulate microglial function and contribute to neuroprotection (ref: Schlotterose doi.org/10.3390/antiox12061248/). This study aligns with findings from Liu et al., who demonstrated that various stimuli, including LPS, induce significant metabolic shifts in microglia, promoting glycolysis while inhibiting oxidative phosphorylation (ref: Liu doi.org/10.3390/molecules28114501/). Such metabolic reprogramming may exacerbate neuroinflammatory responses, further complicating AD pathology. Additionally, the synthesis of thieno[3,2-c]pyrazol-3-amine derivatives as glycogen synthase kinase 3β inhibitors by Yan et al. underscores the potential for targeting metabolic pathways in microglia as a therapeutic strategy for AD (ref: Yan doi.org/10.1016/j.bioorg.2023.106663/). Furthermore, Ni et al. demonstrated that electroacupuncture can ameliorate cognitive impairment and beta-amyloid pathology by inhibiting NLRP3 inflammasome activation, suggesting that non-invasive interventions may effectively regulate microglial activation and metabolism (ref: Ni doi.org/10.1016/j.heliyon.2023.e16755/). These studies collectively emphasize the intricate relationship between microglial activation, metabolism, and their implications for AD pathology.

Neuroinflammation and the immune response play critical roles in the progression of Alzheimer's disease (AD), with recent studies elucidating the mechanisms involved. Ospondpant et al. demonstrated that extracts from Dracaena cochinchinensis significantly suppress inflammatory responses and phagocytosis in activated microglial cells, indicating potential therapeutic applications for natural products in managing neuroinflammation (ref: Ospondpant doi.org/10.1016/j.phymed.2023.154936/). This finding aligns with Bieger et al.'s work on neuroinflammation biomarkers within the AT(N) framework, which highlights the importance of inflammatory changes in AD and their potential as diagnostic markers (ref: Bieger doi.org/10.14283/jpad.2023.54/). Moreover, Zhou et al. explored the role of complement C3 in enhancing LPS-elicited neuroinflammation and neurodegeneration via the Mac1/NOX2 pathway, providing insights into how complement activation contributes to chronic neuroinflammation in AD (ref: Zhou doi.org/10.1007/s12035-023-03393-w/). Additionally, Medina-Vera et al. evaluated the expression of endocannabinoid receptors during AD progression, revealing their potential role in modulating neuroinflammatory responses (ref: Medina-Vera doi.org/10.3390/biology12060805/). Collectively, these studies emphasize the complex interplay between neuroinflammation and immune responses in AD, highlighting potential therapeutic targets for intervention.