Recent advancements in the identification of biomarkers for Alzheimer's disease (AD) have highlighted the significance of soluble tau assemblies and plasma biomarkers in early diagnosis and monitoring of disease progression. A study by Islam et al. emphasizes the potential of phospho-tau serine-262 and serine-356 as biomarkers for pre-tangle soluble tau assemblies, suggesting that targeting these intermediates could provide therapeutic benefits before the formation of neurofibrillary tangles (ref: Islam doi.org/10.1038/s41591-024-03400-0/). In another study, Yun et al. explored the temporal dynamics of various Alzheimer biomarkers, revealing that the p-tau217+/Aβ PET- group exhibited significantly lower hippocampal volumes and a worse clinical trajectory compared to their counterparts, indicating the importance of discordance between plasma biomarkers and PET results (ref: Yun doi.org/10.1001/jamaneurol.2024.5263/). VandeVrede et al. further supported these findings by demonstrating that plasma p-tau217 concentrations were significantly higher in AD-related syndromes compared to frontotemporal lobar degeneration (FTLD) syndromes, reinforcing the utility of plasma biomarkers in distinguishing between different neurodegenerative conditions (ref: VandeVrede doi.org/10.1001/jamaneurol.2024.5017/). Additionally, Anastasi et al. conducted a head-to-head comparison of plasma biomarkers, finding that p-tau217 consistently outperformed other assays in detecting Aβ pathology, underscoring its potential as a reliable surrogate for cerebrospinal fluid biomarkers (ref: Anastasi doi.org/10.1002/alz.14609/). Cogswell et al. also highlighted the utility of plasma %p-tau217 as a screening tool for identifying individuals at risk of progressing to abnormal amyloid PET results, suggesting its application in primary prevention trials (ref: Cogswell doi.org/10.1002/alz.14629/). Overall, these studies collectively underscore the evolving landscape of blood-based biomarkers in AD, emphasizing their diagnostic potential and the need for further validation in clinical settings.

The pathophysiology of Alzheimer's disease (AD) is increasingly understood through the lens of neuroinflammation and cellular mechanisms. McManus et al. investigated the role of the NLRP3 inflammasome in AD, demonstrating that Aβ deposition activates NLRP3 in APP/PS1 mice, suggesting a critical link between inflammation and disease progression (ref: McManus doi.org/10.1016/j.immuni.2025.01.007/). In parallel, Fröhlich et al. elucidated the role of TYK2 in tau phosphorylation, revealing that TYK2-mediated phosphorylation at tyrosine 29 promotes tau aggregation by impairing autophagic clearance, thereby contributing to tau pathology (ref: Fröhlich doi.org/10.1016/j.tins.2025.01.004/). Furthermore, Khawaja et al. highlighted the decline of chaperone-mediated autophagy (CMA) with aging, linking its dysfunction to the progression of AD and suggesting that enhancing CMA could mitigate age-related neurodegenerative diseases (ref: Khawaja doi.org/10.1038/s43587-024-00799-6/). The interplay between neuroinflammation and tau pathology is further supported by findings from Yang et al., who demonstrated that astrocytic EphA4 signaling is crucial for the elimination of excitatory synapses in AD, indicating that astrocytes play a significant role in synaptic maintenance and neurodegeneration (ref: Yang doi.org/10.1073/pnas.2420324122/). Collectively, these studies underscore the multifaceted nature of AD pathophysiology, highlighting the importance of neuroinflammatory pathways and cellular mechanisms in the disease's progression.

Genetic and epigenetic factors play a pivotal role in the development and progression of Alzheimer's disease (AD). Liu et al. conducted a comprehensive analysis of autosomal-dominant AD, identifying 550 genetic variants associated with the disease, of which 279 were classified as pathogenic. This study provided insights into the global distribution and age of onset of these variants, emphasizing the need for genetic screening in at-risk populations (ref: Liu doi.org/10.1093/brain/). Willett et al. expanded on this by identifying 16 novel AD loci through multi-ancestry meta-analyses, highlighting the importance of including diverse populations in genetic studies to uncover additional risk factors (ref: Willett doi.org/10.1002/alz.14592/). Arnold et al. proposed the concept of individual bioenergetic capacity as a potential source of resilience against AD, suggesting that variations in metabolic resilience could influence disease onset and progression (ref: Arnold doi.org/10.1038/s41467-025-57032-0/). Additionally, Dittrich et al. evaluated plasma-based proteotyping assays against APOE ε4 genotyping, demonstrating high sensitivity and specificity for identifying individuals at risk for AD, thus providing a practical tool for clinical settings (ref: Dittrich doi.org/10.1002/alz.14610/). Kouhsar et al. further explored the epigenetic landscape by analyzing DNA methylation patterns associated with psychosis in AD, revealing significant co-methylated loci that may contribute to the disease's neurobiological underpinnings (ref: Kouhsar doi.org/10.1002/alz.14501/). Together, these studies underscore the intricate interplay between genetic, epigenetic, and metabolic factors in AD, paving the way for personalized approaches to prevention and treatment.

Environmental and lifestyle factors significantly influence the risk and progression of Alzheimer's disease (AD). Dong et al. conducted a nationwide retrospective cohort study that linked air pollution exposure to increased mortality and hospital readmission rates among Medicare beneficiaries with AD and related dementias, suggesting that fine particulate matter (PM2.5) may exacerbate disease outcomes (ref: Dong doi.org/10.1016/S2542-5196(25)00001-4/). Ramey et al. further explored the relationship between autoimmune disorders and AD risk, finding that individuals with autoimmune conditions had a 1.4 to 1.7 times higher odds of developing AD, particularly among those with endocrine and gastrointestinal disorders (ref: Ramey doi.org/10.1016/j.xcrm.2025.101980/). Grill et al. examined the psychological impact of disclosing elevated amyloid status to cognitively unimpaired individuals, finding no association with long-term suicidality, which suggests that such disclosures may not adversely affect mental health (ref: Grill doi.org/10.1002/alz.14623/). Additionally, Chen et al. constructed a single-nucleus transcriptome atlas of the basal forebrain, revealing age-related changes that could inform lifestyle interventions aimed at preserving cognitive function (ref: Chen doi.org/10.1093/brain/). Collectively, these studies highlight the critical role of environmental exposures and lifestyle factors in shaping AD risk, emphasizing the need for public health strategies aimed at mitigating these risks.

Innovative therapeutic approaches for Alzheimer's disease (AD) are being explored, focusing on personalized medicine and neuroregenerative strategies. Menendez-Gonzalez et al. introduced a tridimensional diagnostic framework that integrates genetic, molecular, and neuroanatomical factors to enhance the precision of AD diagnostics and treatment (ref: Menendez-Gonzalez doi.org/10.1002/alz.14591/). Wu et al. reported promising results from a brain-wide neuroregenerative gene therapy that significantly improved cognitive functions in a mouse model of AD, demonstrating the potential for regenerative medicine to reverse cognitive decline (ref: Wu doi.org/10.1002/advs.202410080/). Furthermore, Damsgaard et al. highlighted the occupational impacts of young-onset Alzheimer's disease (YOAD), revealing that patients experienced significant increases in sick leave and unemployment rates prior to diagnosis, which underscores the need for early intervention strategies (ref: Damsgaard doi.org/10.1002/alz.14607/). Ko et al. examined the paradoxical effects of midlife cognitive activity on tau-related cognitive impairment, suggesting that while cognitive engagement is generally beneficial, it may accelerate decline in already impaired individuals (ref: Ko doi.org/10.1002/alz.14606/). These findings collectively emphasize the importance of developing targeted therapeutic interventions that consider individual patient profiles and the timing of interventions to optimize outcomes in AD.

Neuroinflammation and the immune response are critical components in the pathogenesis of Alzheimer's disease (AD). Fixemer et al. characterized distinct microglial aggregates in the AD hippocampus, identifying plaque-associated microglia and coffin-like microglia that play significant roles in disease progression, including engulfing neurons and associating with tau pathology (ref: Fixemer doi.org/10.1007/s00401-025-02857-8/). Yang et al. further elucidated the role of astrocytic EphA4 signaling in synapse elimination, demonstrating that knockout of EphA4 in astrocytes mitigated excitatory synapse loss in AD models, highlighting the importance of astrocytes in maintaining synaptic integrity (ref: Yang doi.org/10.1073/pnas.2420324122/). Chen et al. explored the transition-state-dependent generation of reactive oxygen species by Aβ assemblies, proposing a self-regulated feedback loop that contributes to aggregate formation and toxicity, thus linking oxidative stress to neuroinflammation (ref: Chen doi.org/10.1021/jacs.4c15532/). These studies collectively underscore the complex interplay between neuroinflammatory processes and neurodegeneration in AD, suggesting that targeting these pathways may offer new therapeutic avenues.

Cognitive decline in Alzheimer's disease (AD) is a multifaceted process influenced by various neurobiological and psychosocial factors. Chen et al. constructed a single-nucleus transcriptome atlas of the basal forebrain, revealing age-related changes that could inform interventions aimed at preserving cognitive function (ref: Chen doi.org/10.1093/brain/). Xu et al. developed a tracer kinetic model to assess blood-brain barrier (BBB) permeability in AD and dementia with Lewy bodies, finding heterogeneous patterns of BBB breakdown that correlated with clinical severity, which may impact cognitive outcomes (ref: Xu doi.org/10.1002/alz.14529/). Kouhsar et al. conducted a brain DNA co-methylation network analysis, identifying modules associated with psychosis in AD, which may provide insights into the neuropsychological aspects of the disease (ref: Kouhsar doi.org/10.1002/alz.14501/). Damsgaard et al. highlighted the occupational impacts of young-onset Alzheimer's disease (YOAD), revealing significant increases in sick leave and unemployment rates prior to diagnosis, emphasizing the need for early intervention strategies (ref: Damsgaard doi.org/10.1002/alz.14607/). Additionally, Duggan et al. introduced the Dementia SomaSignal Test (dSST), a plasma proteomic predictor of dementia risk, which could serve as a valuable tool for identifying individuals at risk of cognitive decline over the long term (ref: Duggan doi.org/10.1002/alz.14549/). Together, these studies illustrate the complex interplay between biological, psychological, and social factors in cognitive decline associated with AD.

Aging is a significant risk factor for Alzheimer's disease (AD), influencing both the onset and progression of the condition. Khawaja et al. examined the decline of chaperone-mediated autophagy (CMA) with age, linking its dysfunction to the progression of AD and suggesting that enhancing CMA could mitigate age-related neurodegenerative diseases (ref: Khawaja doi.org/10.1038/s43587-024-00799-6/). Xu et al. developed a tracer kinetic model to assess blood-brain barrier (BBB) permeability in AD, revealing heterogeneous patterns of BBB breakdown that correlated with clinical severity, which may impact cognitive outcomes (ref: Xu doi.org/10.1002/alz.14529/). Damsgaard et al. highlighted the occupational impacts of young-onset Alzheimer's disease (YOAD), revealing significant increases in sick leave and unemployment rates prior to diagnosis, emphasizing the need for early intervention strategies (ref: Damsgaard doi.org/10.1002/alz.14607/). Kouhsar et al. conducted a brain DNA co-methylation network analysis, identifying modules associated with psychosis in AD, which may provide insights into the neuropsychological aspects of the disease (ref: Kouhsar doi.org/10.1002/alz.14501/). Additionally, Duggan et al. introduced the Dementia SomaSignal Test (dSST), a plasma proteomic predictor of dementia risk, which could serve as a valuable tool for identifying individuals at risk of cognitive decline over the long term (ref: Duggan doi.org/10.1002/alz.14549/). Collectively, these studies underscore the intricate relationship between aging and AD, highlighting the need for targeted interventions that address age-related vulnerabilities.