In addition to these findings, Smith et al. utilized single-nuclei RNA sequencing to characterize the transcriptional responses of microglia and astrocytes in AD, identifying distinct gene expression patterns associated with amyloid and tau pathologies (ref: Smith doi.org/10.1007/s00401-021-02372-6/). This study underscores the complexity of glial responses in AD and highlights the differential roles of these cell types in disease progression. Wang et al. further elucidated the mechanisms by which the Nogo receptor impairs microglial clearance of Aβ, linking this impairment to accelerated disease progression (ref: Wang doi.org/10.1111/acel.13515/). Lastly, Machhi et al. demonstrated that CD4+ effector T cells can exacerbate AD pathology in mouse models, suggesting that both innate and adaptive immune responses are integral to the disease process (ref: Machhi doi.org/10.1186/s12974-021-02308-7/). Collectively, these studies reveal the multifaceted roles of microglia in AD, emphasizing the interplay between metabolic, immune, and transcriptional factors in the disease's progression.

Chen et al. introduced a novel sporadic AD animal model using acrolein, which induced classic AD pathologies, thus providing a new platform for studying neuroinflammation and its effects on cognitive decline (ref: Chen doi.org/10.1016/j.phrs.2021.106003/). Furthermore, Cheng et al. explored the role of the NLRP3 inflammasome in myocardial infarction-induced neurodegeneration, suggesting that systemic inflammation can influence neurodegenerative processes (ref: Cheng doi.org/10.21037/atm-21-4931/). Yan et al. investigated the neuroprotective effects of adiponectin in 3xTg-AD mice, finding that it ameliorates cognitive deficits and neuroinflammation, thereby highlighting the potential of metabolic regulators in modulating neuroinflammatory responses (ref: Yan doi.org/10.3233/JAD-215063/). Lastly, Das et al. examined the relationship between neural network dysfunction and microglial alterations, revealing that interventions to suppress epileptiform activity can reverse aberrant microglial gene expression, further linking neuroinflammation to cognitive impairment in AD (ref: Das doi.org/10.1016/j.isci.2021.103245/). Together, these studies emphasize the critical role of neuroinflammation in AD and the potential for targeting immune pathways to mitigate disease progression.

Additionally, Palmer et al. utilized single-nucleus RNA sequencing to investigate cellular and molecular alterations in Down syndrome brains, which are prone to developing AD-like pathology, thereby providing insights into the genetic and environmental factors influencing AD (ref: Palmer doi.org/10.1073/pnas.2114326118/). Sun et al. explored the effects of Dihexa, an angiotensin IV analog, on cognitive impairment in APP/PS1 mice, demonstrating its potential to rescue memory deficits through the PI3K/AKT signaling pathway (ref: Sun doi.org/10.3390/brainsci11111487/). Lastly, Bowers et al. assessed the impact of tart cherry extract and omega fatty acids on behavioral deficits and amyloid-beta deposition in the 5xFAD mouse model, suggesting that dietary interventions may mitigate AD-like symptoms (ref: Bowers doi.org/10.3390/brainsci11111423/). Collectively, these studies underscore the importance of diverse animal models in elucidating the mechanisms of AD and evaluating novel therapeutic approaches.

Moreover, Jin et al. investigated the role of GPR17 in mediating Aβ-induced cognitive deficits, suggesting that targeting this receptor could mitigate neurotoxicity associated with AD (ref: Jin doi.org/10.1016/j.intimp.2021.108335/). Wu et al. focused on SIRT5, demonstrating its role in repressing neurotrophic pathways and Aβ production by targeting autophagy, thus linking autophagic processes to AD pathology (ref: Wu doi.org/10.1021/acschemneuro.1c00468/). Additionally, Wu et al. explored the anti-inflammatory effects of an oligomannuronic acid-sialic acid conjugate, which inhibited Aβ aggregation and reduced microglial inflammatory responses (ref: Wu doi.org/10.3390/ijms222212338/). These findings collectively enhance our understanding of the molecular pathways involved in AD and highlight potential targets for therapeutic intervention.

Furthermore, Fu et al. reported that rhynchophylline administration improves amyloid-beta pathology and inflammation in an AD transgenic mouse model, indicating its potential as a novel therapeutic agent (ref: Fu doi.org/10.1021/acschemneuro.1c00600/). Solleiro-Villavicencio et al. examined the effects of chronic ozone exposure on interleukin 17A expression during neurodegeneration, suggesting that environmental factors may influence inflammatory responses in AD (ref: Solleiro-Villavicencio doi.org/10.1016/j.nrleng.2018.08.003/). Lastly, Liu et al. explored the effects of modulating gamma oscillations through repetitive transcranial magnetic stimulation, finding significant improvements in cognitive function among AD patients (ref: Liu doi.org/10.1093/cercor/). Collectively, these studies underscore the diverse strategies being explored to address the multifaceted challenges of AD.

Kummer et al. further explored the PD-1/PD-L1 immune checkpoint pathway, revealing that astrocytic PD-L1 can stimulate microglial PD-1, thereby suppressing neuroinflammation and AD pathology (ref: Kummer doi.org/10.15252/embj.2021108662/). This interplay between astrocytes and microglia underscores the complexity of neuroinflammatory responses in AD and suggests potential therapeutic targets that could enhance astrocytic support for microglial function. Collectively, these studies emphasize the critical role of astrocyte-microglia interactions in modulating neuroinflammation and highlight the potential for targeting these pathways to improve outcomes in AD.