Research on Alzheimer's disease (AD) pathology and biomarkers has made significant strides, particularly in understanding amyloid-beta (Aβ) and tau dynamics. A study by Milà-Alomà et al. identified plasma phosphorylated tau231 (p-tau231) and p-tau217 as effective biomarkers for early Aβ pathology, suggesting their utility in preclinical AD trials (ref: Milà-Alomà doi.org/10.1038/s41591-022-01925-w/). This aligns with findings from Ozlen et al., who explored the spatial extent of Aβ levels and their correlation with tau-PET imaging and cognitive decline, emphasizing the importance of early detection in preventive trials (ref: Ozlen doi.org/10.1001/jamaneurol.2022.2442/). Furthermore, Traxler et al. revealed a metabolic shift to aerobic glycolysis in induced neurons from AD patients, indicating a potential metabolic pathway involved in AD pathology (ref: Traxler doi.org/10.1016/j.cmet.2022.07.014/). Contradictory findings emerged from Frontzkowski et al., who noted that younger onset of AD is linked to accelerated tau pathology, suggesting that age-related factors may complicate the interpretation of biomarker efficacy (ref: Frontzkowski doi.org/10.1038/s41467-022-32592-7/). Overall, these studies highlight the complex interplay between metabolic changes, tau and Aβ pathology, and the potential for blood-based biomarkers in early AD detection and intervention.

The genetic landscape of Alzheimer's disease (AD) has been further elucidated through various studies focusing on microglial function and regulatory variants. Silvin et al. provided insights into the dual ontogeny of microglia and macrophages, emphasizing their roles in neurodegeneration and the need for a better understanding of their phenotypic variations (ref: Silvin doi.org/10.1016/j.immuni.2022.07.004/). Cooper et al. identified 320 functional regulatory variants associated with AD and progressive supranuclear palsy, underscoring the complexity of genetic contributions to neurodegeneration (ref: Cooper doi.org/10.1126/science.abi8654/). Additionally, Zhang et al. explored the interaction between apolipoprotein E (APOE) and ACE2 in the context of COVID-19, revealing how APOE4 carriers may experience heightened inflammatory responses, which could exacerbate AD pathology (ref: Zhang doi.org/10.1038/s41392-022-01118-4/). These findings collectively suggest that genetic predispositions, particularly involving APOE, play a critical role in AD risk and progression, while also highlighting the potential for therapeutic interventions targeting these pathways.

Neuroinflammation remains a pivotal area of research in understanding Alzheimer's disease (AD), with studies revealing the intricate roles of microglia and astrocytes. Kosoy et al. conducted a comprehensive analysis of the genetic regulome of human microglia, identifying regulatory mechanisms linked to 21 AD risk loci, which could inform future therapeutic strategies (ref: Kosoy doi.org/10.1038/s41588-022-01149-1/). Margeta et al. investigated the neurodegenerative phenotype of microglia in glaucoma models, finding that APOE4 influences microglial responses, potentially linking neuroinflammation to both AD and glaucoma (ref: Margeta doi.org/10.1016/j.immuni.2022.07.014/). Furthermore, Lee et al. demonstrated that Aβ42 oligomers induce synaptic loss through CAMKK2-AMPK pathways, highlighting a mechanism by which neuroinflammation contributes to synaptic dysfunction in AD (ref: Lee doi.org/10.1038/s41467-022-32130-5/). These studies collectively underscore the dual role of neuroinflammation as both a contributor to and a potential target for therapeutic intervention in AD.

Recent advancements in therapeutic strategies for Alzheimer's disease (AD) have focused on targeting specific pathways and mechanisms underlying the disease. Cuddy et al. demonstrated that the farnesyltransferase inhibitor LNK-754 significantly reduced amyloid plaque burden and tau hyperphosphorylation in the 5XFAD mouse model, suggesting a promising avenue for drug development (ref: Cuddy doi.org/10.1186/s13024-022-00561-9/). In parallel, Victor et al. explored the impact of APOE4 on microglial surveillance, revealing that lipid accumulation impairs microglial function, which could be a target for therapeutic intervention (ref: Victor doi.org/10.1016/j.stem.2022.07.005/). Additionally, Ortí-Casañ et al. highlighted the neuroprotective potential of TNF receptor 2 agonists, which ameliorated neuropathology and improved cognition in mouse models, indicating that modulation of inflammatory pathways may offer therapeutic benefits (ref: Ortí-Casañ doi.org/10.1073/pnas.2201137119/). These findings reflect a growing recognition of the need for multifaceted approaches that address both neuroinflammatory and amyloid-related pathways in AD treatment.

Understanding the mechanisms of neurodegeneration in Alzheimer's disease (AD) has been advanced through various innovative models and methodologies. Kang et al. highlighted the efficacy of plasma exchange in removing neurotoxic lipophilic chemicals, demonstrating its potential to slow disease progression in AD patients (ref: Kang doi.org/10.1002/alz.12739/). Furthermore, Barisano et al. conducted a multi-omics analysis revealing how APOE4 affects blood-brain barrier integrity and synaptic function, providing insights into the molecular underpinnings of AD pathology (ref: Barisano doi.org/10.1084/jem.20221137/). Prissette et al. investigated the disruption of nuclear envelope integrity as a potential initiating event in tauopathies, suggesting that cellular perturbations may precede tau aggregation (ref: Prissette doi.org/10.1016/j.celrep.2022.111249/). These studies collectively emphasize the importance of exploring diverse mechanisms and models to unravel the complexities of neurodegeneration in AD.

Research into cognitive decline and behavioral symptoms in Alzheimer's disease (AD) has revealed critical insights into the interplay between genetic factors and neurovascular health. Liu et al. demonstrated that peripheral apoE4 exacerbates AD pathology and cognitive impairment by compromising cerebrovascular function, highlighting the significance of the blood-brain barrier in disease progression (ref: Liu doi.org/10.1038/s41593-022-01127-0/). Additionally, Ortí-Casañ et al. explored the role of TNF receptor 2 in ameliorating neuropathology and improving cognition in mouse models, suggesting that targeting inflammatory pathways could enhance cognitive outcomes (ref: Ortí-Casañ doi.org/10.1073/pnas.2201137119/). These findings underscore the multifactorial nature of cognitive decline in AD, where both genetic predispositions and neuroinflammatory responses play crucial roles in shaping cognitive trajectories.

The impact of environmental and lifestyle factors on Alzheimer's disease (AD) has garnered increasing attention, particularly regarding air pollution and sedentary behavior. Ma et al. found that long-term exposure to ambient air pollution is associated with cognitive decline and increased amyloid pathology, emphasizing the need for public health interventions to mitigate environmental risks (ref: Ma doi.org/10.1016/j.biopsych.2022.05.017/). In a related study, Raichlen et al. reported that leisure-time sedentary behaviors differentially affect dementia risk, with television viewing linked to increased risk while computer use was associated with decreased risk, suggesting that the type of sedentary behavior may have varying implications for cognitive health (ref: Raichlen doi.org/10.1073/pnas.2206931119/). These findings highlight the importance of considering lifestyle factors in AD prevention and intervention strategies.

Neuroimaging techniques have become essential tools in the early diagnosis and monitoring of Alzheimer's disease (AD). Insel et al. demonstrated the utility of tau positron emission tomography (PET) in preclinical AD, identifying specific brain regions where tau accumulation correlates with cognitive decline (ref: Insel doi.org/10.1093/brain/). Ozlen et al. further explored the spatial extent of amyloid-beta levels and their associations with tau-PET and cognition, emphasizing the importance of early biomarker detection in clinical trials (ref: Ozlen doi.org/10.1001/jamaneurol.2022.2442/). Additionally, Ortí-Casañ et al. highlighted the potential of TNF receptor 2 agonists in ameliorating neuropathology, suggesting that neuroimaging could play a role in assessing treatment efficacy (ref: Ortí-Casañ doi.org/10.1073/pnas.2201137119/). Collectively, these studies underscore the critical role of neuroimaging in advancing our understanding of AD pathology and improving diagnostic accuracy.