Recent studies have elucidated various molecular mechanisms and pathways involved in Alzheimer's disease (AD) progression. One significant finding is the role of the triggering receptor expressed on myeloid cells 2 (TREM2) in modulating microglial responses to AD pathology. Zhou et al. employed single-nucleus RNA sequencing to reveal TREM2-dependent and independent cellular responses in both human and mouse models of AD, highlighting the complexity of glial involvement in disease progression (ref: Zhou doi.org/10.1038/s41591-019-0695-9/). Additionally, Bai et al. utilized mass spectrometry to profile over 14,000 proteins in the human brain, identifying 173 protein changes across 17 pathways associated with AD, thus providing insights into the molecular networks that characterize different stages of the disease (ref: Bai doi.org/10.1016/j.neuron.2019.12.015/). Furthermore, Zhang et al. demonstrated that β-amyloid redirects norepinephrine signaling to activate the GSK3β/tau cascade, linking two critical pathological components of AD (ref: Zhang doi.org/10.1126/scitranslmed.aay6931/). These findings collectively underscore the intricate interplay between various molecular pathways and their contributions to AD pathology, suggesting potential targets for therapeutic intervention. Moreover, the dysregulation of metabolic networks has emerged as a critical aspect of AD pathogenesis. Mahajan et al. reported significant abnormalities in brain transmethylation and polyamine pathways, indicating a broader metabolic disorder associated with AD (ref: Mahajan doi.org/10.1371/journal.pmed.1003012/). In a related context, Zheng et al. highlighted the impact of phosphorylated tau accumulation in GABAergic interneurons, which impaired adult hippocampal neurogenesis, further complicating the neurogenic landscape in AD (ref: Zheng doi.org/10.1016/j.stem.2019.12.015/). The cumulative evidence from these studies emphasizes the multifaceted nature of AD, where molecular, metabolic, and neurogenic factors converge to influence disease progression.

Neuroinflammation plays a pivotal role in the pathophysiology of Alzheimer's disease (AD), with recent studies shedding light on the immune response mechanisms involved. Allnutt et al. investigated the presence of human herpesvirus 6 (HHV-6) in AD cases and controls, revealing a potential link between viral infections and neuroinflammation in AD pathology (ref: Allnutt doi.org/10.1016/j.neuron.2019.12.031/). This study adds to the growing body of literature suggesting that viral infections may exacerbate neuroinflammatory processes, although establishing causality remains challenging. Concurrently, Das et al. explored the phagocytic activity of activated microglia towards tau oligomers, demonstrating that microglial activation can lead to a destructive inflammatory state, further contributing to neurodegeneration (ref: Das doi.org/10.1186/s12974-019-1694-y/). In addition to viral contributions, the impact of systemic factors on neuroinflammation has been highlighted. Sankar et al. examined the interplay between diabetes and AD, finding that diabetic conditions can stimulate cytokine expression and enhance neuroinflammatory responses in an AD mouse model (ref: Sankar doi.org/10.1186/s12974-020-1707-x/). Furthermore, Iturria-Medina et al. demonstrated that blood and brain gene expression trajectories mirror neuropathology and cognitive decline, suggesting that peripheral inflammatory markers may serve as indicators of neuroinflammatory processes in the brain (ref: Iturria-Medina doi.org/10.1093/brain/). Collectively, these studies underscore the critical role of neuroinflammation in AD, highlighting both intrinsic and extrinsic factors that may influence disease progression and cognitive decline.

Cognitive decline in Alzheimer's disease (AD) is a multifaceted process influenced by various neurobiological and psychosocial factors. Recent research has underscored the importance of structural brain changes, particularly hippocampal volume, in predicting cognitive decline. Dawe et al. found that hippocampal volume accounted for a significant portion of the variance in cognitive decline rates, independent of traditional neuropathological indices, suggesting its critical role in cognitive health during aging (ref: Dawe doi.org/10.1002/alz.12009/). This finding aligns with the broader understanding that structural brain integrity is essential for maintaining cognitive function in older adults. Moreover, the association between depression and subsequent dementia diagnosis has been a focal point of investigation. Holmquist et al. reported that individuals diagnosed with depression exhibited significantly increased odds of developing dementia, particularly within the first six months post-diagnosis, highlighting the potential for early intervention strategies to mitigate cognitive decline (ref: Holmquist doi.org/10.1371/journal.pmed.1003016/). Additionally, Jia et al. provided insights into the genetic underpinnings of familial AD, identifying mutations in PSEN1, PSEN2, and APP across Chinese pedigrees, which may contribute to cognitive decline in affected individuals (ref: Jia doi.org/10.1002/alz.12005/). Together, these studies illustrate the complex interplay between structural brain changes, genetic factors, and psychosocial influences in the trajectory of cognitive decline associated with AD.

Genetic factors and biomarkers play a crucial role in understanding Alzheimer's disease (AD) and its progression. Recent studies have focused on the apolipoprotein E (APOE) genotype, particularly the APOE ε4 allele, which is a well-established risk factor for AD. Hunter et al. investigated the association between APOE ε4 status and cognitive performance in amateur soccer players, finding no direct link between the allele and verbal memory, suggesting that other factors may mediate cognitive outcomes in this population (ref: Hunter doi.org/10.1001/jamaneurol.2019.4828/). This highlights the complexity of genetic influences on cognition, particularly in physically active individuals. In a broader context, Pathak et al. conducted a two-stage Bayesian genome-wide association study (GWAS) to identify single-nucleotide polymorphisms (SNPs) associated with inverse comorbidity of AD and age-related cancers, revealing potential genetic overlaps that could inform future research on AD risk (ref: Pathak doi.org/10.1002/alz.12003/). Furthermore, Lussier et al. examined mild behavioral impairment (MBI) in cognitively intact elderly individuals, establishing a link between MBI and early AD biomarkers, thus supporting the use of MBI as a potential metric for early detection of AD pathology (ref: Lussier doi.org/10.1002/alz.12007/). These findings collectively emphasize the significance of genetic factors and biomarkers in elucidating the pathophysiology of AD and highlight their potential utility in early diagnosis and intervention strategies.

Therapeutic approaches for Alzheimer's disease (AD) are increasingly focusing on innovative strategies to address the underlying pathophysiology of the disease. Mahajan et al. conducted a targeted metabolomic and transcriptomic study, revealing dysregulation in brain transmethylation and polyamine pathways associated with AD, which may present novel therapeutic targets for intervention (ref: Mahajan doi.org/10.1371/journal.pmed.1003012/). This study underscores the potential for metabolic modulation as a therapeutic strategy in AD management. Additionally, Liu et al. introduced a zwitterionic nanoparticle designed to normalize dysfunctional microglial activity and facilitate amyloid-β clearance, representing a promising avenue for AD treatment by targeting the immune response (ref: Liu doi.org/10.1002/advs.201901555/). Furthermore, Gunesch et al. explored the neuroprotective effects of natural products, specifically 7-O-esters of taxifolin, demonstrating their potential in ameliorating neuroinflammation and short-term memory impairment in vivo (ref: Gunesch doi.org/10.1016/j.redox.2019.101378/). These findings highlight the importance of developing multifaceted therapeutic strategies that address both neuroinflammatory and metabolic aspects of AD, paving the way for more effective interventions. Moreover, Herring et al. evaluated the efficacy of suvorexant, an orexin receptor antagonist, in treating insomnia in patients with probable AD dementia, finding significant improvements in total sleep time (ref: Herring doi.org/10.1002/alz.12035/). This emphasizes the importance of addressing comorbid conditions, such as sleep disturbances, in the holistic management of AD. Collectively, these studies reflect a growing recognition of the need for innovative therapeutic approaches that target the complex interplay of factors contributing to AD pathology.

Environmental and lifestyle factors have been increasingly recognized as significant contributors to the risk and progression of Alzheimer's disease (AD). Kulick et al. investigated the impact of long-term exposure to ambient air pollution on cognitive decline, finding that higher levels of nitrogen dioxide were associated with accelerated cognitive deterioration among older adults, particularly in those with APOE ε4 status (ref: Kulick doi.org/10.1016/j.envint.2019.105440/). This study underscores the importance of environmental factors in shaping cognitive health and highlights the need for public health interventions to mitigate air pollution exposure. In addition to environmental influences, psychosocial factors such as depression have been shown to correlate with increased dementia risk. Holmquist et al. reported that individuals with a history of depression had significantly higher odds of developing dementia, particularly shortly after their depression diagnosis, suggesting that effective management of depression could be crucial in reducing dementia risk (ref: Holmquist doi.org/10.1371/journal.pmed.1003016/). Furthermore, Burke et al. mapped migraine to a common brain network, providing insights into the potential shared neurobiological pathways between migraine and cognitive decline, which may inform lifestyle modifications for at-risk populations (ref: Burke doi.org/10.1093/brain/). These findings collectively highlight the multifactorial nature of AD, where environmental exposures, lifestyle choices, and psychosocial factors converge to influence cognitive health. Addressing these factors through targeted interventions may offer new avenues for preventing or delaying the onset of AD.

Neuroimaging and biomarker studies are pivotal in advancing our understanding of Alzheimer's disease (AD) and its progression. Meyer et al. characterized discrepancies in AD biomarkers using cerebrospinal fluid (CSF) phosphorylated tau and positron emission tomography (PET), revealing that individuals with elevated CSF tau levels experienced faster cognitive decline compared to those with negative biomarker profiles (ref: Meyer doi.org/10.1001/jamaneurol.2019.4749/). This suggests that CSF tau accumulation may precede PET positivity, providing critical insights into the temporal dynamics of AD pathology. In a related study, Zeydan et al. examined the association of amyloid PET imaging with age in multiple sclerosis patients, finding that the rate of amyloid accumulation was steeper in healthy controls compared to MS patients (ref: Zeydan doi.org/10.1002/ana.25684/). This highlights the potential for neuroimaging to differentiate between AD and other neurodegenerative conditions, enhancing diagnostic accuracy. Additionally, Bai et al. employed deep multilayer brain proteomics to identify molecular networks associated with AD progression, validating their findings across independent cohorts and emphasizing the role of protein alterations in disease pathogenesis (ref: Bai doi.org/10.1016/j.neuron.2019.12.015/). Furthermore, Gunesch et al. explored the neuroprotective effects of natural products, demonstrating their potential in ameliorating neuroinflammation and cognitive impairment, which may serve as complementary strategies alongside neuroimaging and biomarker assessments (ref: Gunesch doi.org/10.1016/j.redox.2019.101378/). Collectively, these studies underscore the importance of integrating neuroimaging and biomarker research to enhance our understanding of AD and inform future therapeutic strategies.