Microglia play a crucial role in the pathophysiology of Alzheimer's disease (AD), particularly in their interaction with amyloid plaques and synaptic changes. Recent studies have utilized various mouse models to elucidate the effects of microglial dysfunction on AD progression. For instance, Lall et al. demonstrated that microglial C9ORF72 deficiency in mice leads to significant alterations in neuroinflammatory responses, which may not fully translate to human conditions (ref: Chen-Plotkin doi.org/10.1016/j.neuron.2021.06.031/). Claes et al. further explored the role of TREM2 mutations in human microglial function, revealing that lipid droplet accumulation in plaque-associated microglia correlates with altered transcriptional profiles resembling atherosclerotic foam cells (ref: Claes doi.org/10.1186/s13024-021-00473-0/). Additionally, Benitez et al. validated the relationship between microglial activity and amyloid plaques using knock-in models, showing increased glutamate release prior to plaque formation, suggesting early microglial involvement in synaptic dysfunction (ref: Benitez doi.org/10.1186/s13024-021-00457-0/). These findings collectively highlight the multifaceted role of microglia in AD, emphasizing the need for targeted therapeutic strategies that modulate microglial function to mitigate disease progression. The interplay between microglial autophagy and lipid metabolism has also emerged as a significant area of research. Xu et al. reported that autophagy deficiency in microglia exacerbates tau pathology, indicating that microglial autophagy is essential for maintaining lipid homeostasis and preventing neuroinflammation (ref: Xu doi.org/10.1073/pnas.2023418118/). Furthermore, the therapeutic potential of compounds like Schizandrin A has been investigated, with Wang et al. demonstrating its ability to improve cognitive functions in AD mice by modulating microglial polarization (ref: Wang doi.org/10.1080/13880209.2021.1941132/). This highlights the potential for pharmacological interventions that target microglial activation states to enhance cognitive outcomes in AD. Lastly, Ousta et al. explored microglial activation following cardiac arrest, linking it to neurological injury, thus broadening the understanding of microglial roles beyond AD (ref: Ousta doi.org/10.1007/s12028-021-01253-w/).

Neuroinflammation is increasingly recognized as a pivotal factor in the progression of neurodegenerative diseases, including Alzheimer's disease (AD) and Lewy body diseases (LBDs). Feleke et al. conducted a comprehensive transcriptional profiling study that identified both common and distinct molecular pathologies across PD, PDD, and DLB, underscoring the complexity of neuroinflammatory responses in these conditions (ref: Feleke doi.org/10.1007/s00401-021-02343-x/). In parallel, Emre et al. examined age-related changes in brain phospholipids and bioactive lipids in APP knock-in mice, revealing a significant correlation between lipid profiles, glial activation, and neuroinflammation in aging (ref: Emre doi.org/10.1186/s40478-021-01216-4/). These findings suggest that lipid metabolism may play a critical role in modulating neuroinflammatory responses in AD. Chronic inflammatory conditions, such as colitis, have also been shown to exacerbate neuroinflammation and cognitive decline in middle-aged individuals, as demonstrated by He et al. (ref: He doi.org/10.1186/s12974-021-02199-8/). This highlights the potential for systemic inflammation to influence neurodegenerative processes. Weston et al. further explored the role of interleukin-10 deficiency in tau pathology, finding that the absence of this anti-inflammatory cytokine exacerbates neuroinflammation and tau-related neurodegeneration (ref: Weston doi.org/10.1186/s12974-021-02211-1/). Together, these studies emphasize the intricate relationship between neuroinflammation and neurodegeneration, suggesting that targeting inflammatory pathways may offer therapeutic avenues for mitigating cognitive impairment in AD and related disorders.

The search for effective therapeutic strategies in Alzheimer's disease (AD) has led to the exploration of various novel compounds and approaches. Sun et al. introduced amphiphilic distyrylbenzene derivatives, which demonstrated a high binding affinity for amyloid beta aggregates, showing promise as both therapeutic and imaging agents (ref: Sun doi.org/10.1021/jacs.1c05470/). This innovative approach highlights the potential for dual-function compounds that can aid in both diagnosis and treatment of AD. Additionally, Lim et al. investigated the use of human neural crest-derived nasal turbinate stem cells, finding that their transplantation significantly reduced amyloid levels and improved neuronal survival in a transgenic mouse model of AD (ref: Lim doi.org/10.1186/s13287-021-02489-1/). This suggests that stem cell therapies may offer a viable strategy for addressing the underlying pathology of AD. Moreover, the role of neuroinflammation in AD has prompted the development of anti-inflammatory agents. Kuwar et al. reported on a novel inhibitor targeting the NLRP3 inflammasome, which showed efficacy in reducing neuropathology and improving cognitive function in transgenic mice (ref: Kuwar doi.org/10.3233/JAD-210400/). Similarly, Reading et al. described the design of NE3107, an oral small molecule that modulates neuroinflammation and insulin resistance, and is currently undergoing Phase III clinical trials (ref: Reading doi.org/10.2217/nmt-2021-0022/). These findings collectively underscore the importance of targeting neuroinflammatory pathways as a therapeutic strategy in AD, while also highlighting the need for continued research into the efficacy and safety of emerging treatments.

Understanding the molecular mechanisms underlying Alzheimer's disease (AD) is crucial for developing targeted therapies. Recent studies have focused on the role of epigenetic modifications and autophagy in AD pathogenesis. Li et al. demonstrated that increased methylation of the MEF2A enhancer region leads to decreased expression of autophagy-related genes, which may contribute to the progression of AD (ref: Li doi.org/10.3389/fnins.2021.682247/). This suggests that epigenetic regulation of autophagy could be a potential therapeutic target. In addition, Schober et al. explored the effects of NNC 26-9100 on microglial function, finding that it enhances Aβ phagocytosis while inhibiting nitric oxide production, indicating a potential mechanism for modulating neuroinflammation in AD (ref: Schober doi.org/10.1371/journal.pone.0254242/). Moreover, the role of neuroinflammation in AD has been further elucidated through studies on the NLRP3 inflammasome. Ren et al. highlighted its involvement in neurodegeneration associated with chronic pain, suggesting that targeting this pathway may have broader implications for AD treatment (ref: Ren doi.org/10.1097/SHK.0000000000001832/). Additionally, the identification of SPI1 as a genetic risk factor for AD has opened new avenues for research into how microglial function may be altered in the disease (ref: Jones doi.org/10.1038/s41598-021-94324-z/). Collectively, these studies emphasize the importance of understanding the molecular underpinnings of AD to inform the development of effective therapeutic strategies.

Genetic and environmental factors significantly influence the risk and progression of Alzheimer's disease (AD). Recent studies have highlighted the interplay between genetic predispositions and environmental triggers in modulating neuroinflammation and cognitive decline. For instance, Peng et al. examined the impact of age, hypercholesterolemia, and vitamin D receptor status on β-amyloid accumulation in mice, revealing that these factors collectively exacerbate AD pathology (ref: Peng doi.org/10.1002/bdd.2297/). This underscores the importance of considering both genetic and lifestyle factors in understanding AD risk. Moreover, He et al. demonstrated that chronic colitis exacerbates neuroinflammation and cognitive impairment in middle-aged mice, suggesting that systemic inflammatory conditions can significantly impact brain health and AD progression (ref: He doi.org/10.1186/s12974-021-02199-8/). Zhai et al. further explored the therapeutic potential of exosomal microRNA-22 in ameliorating neuroinflammation and improving neurological function in AD models, indicating that targeting specific molecular pathways may offer new treatment avenues (ref: Zhai doi.org/10.1111/jcmm.16787/). These findings collectively highlight the complex interplay between genetic susceptibility and environmental factors in AD, emphasizing the need for a multifaceted approach to prevention and treatment.

Microglial activation is a critical component of the neuroinflammatory response in Alzheimer's disease (AD), influencing disease progression and neuronal health. Recent studies have focused on the mechanisms underlying microglial activation and its implications for neurodegeneration. Schober et al. demonstrated that NNC 26-9100 enhances Aβ phagocytosis and reduces nitric oxide production in microglial cells, suggesting that modulating microglial function could be a viable therapeutic strategy for AD (ref: Schober doi.org/10.1371/journal.pone.0254242/). Additionally, Xiao et al. found that Tetrahydrocurcumin (THC) ameliorates AD phenotypes by inhibiting microglial cell cycle arrest and apoptosis through Ras/ERK signaling pathways, further supporting the role of microglial modulation in AD treatment (ref: Xiao doi.org/10.1016/j.biopha.2021.111651/). Moreover, Tang et al. identified a new class of anti-neuroinflammatory agents derived from natural products that suppress TLR4/NF-κB/MAPK pathways, highlighting the potential for novel compounds to mitigate microglial activation and neuroinflammation (ref: Tang doi.org/10.1016/j.ejmech.2021.113713/). Furthermore, the study by Li et al. on MEF2A methylation revealed that decreased expression of this gene inhibits autophagy and may contribute to microglial dysfunction in AD (ref: Li doi.org/10.3389/fnins.2021.682247/). These findings collectively emphasize the importance of understanding microglial activation and response mechanisms in developing targeted therapies for AD.

Age-related changes significantly impact the pathophysiology of Alzheimer's disease (AD), influencing both the onset and progression of the disease. Recent research has focused on how aging interacts with genetic and environmental factors to exacerbate AD pathology. Peng et al. investigated the effects of age, hypercholesterolemia, and vitamin D receptor status on β-amyloid accumulation in mice, revealing that these factors collectively heighten the risk of developing AD (ref: Peng doi.org/10.1002/bdd.2297/). This study underscores the critical role of age-related metabolic changes in the accumulation of pathogenic proteins associated with AD. Additionally, Wang et al. explored the effects of Schizandrin A on cognitive functions in aged AD mice, demonstrating that this compound can ameliorate memory deficits and modulate microglial polarization (ref: Wang doi.org/10.1080/13880209.2021.1941132/). This highlights the potential for therapeutic interventions that target age-related changes in microglial function to improve cognitive outcomes in AD. Collectively, these studies emphasize the need for a comprehensive understanding of how aging influences AD pathology, which is essential for developing effective prevention and treatment strategies.