Recent research has highlighted the potential of blood-based biomarkers in diagnosing Alzheimer's disease (AD) and predicting dementia risk. A study demonstrated that elevated levels of phosphorylated tau (p-tau181 and p-tau217), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were significantly associated with an increased hazard for all-cause and AD dementia, showing a non-linear dose-response relationship. These biomarkers exhibited strong predictive performance, with area under the curve values ranging from 70.9% to 82.6%, and negative predictive values exceeding 90%, although positive predictive values were low (ref: Grande doi.org/10.1038/s41591-025-03605-x/). Additionally, a multi-cohort study identified 2,173 dysregulated analytes in cerebrospinal fluid (CSF) across the AD continuum, with a significant portion being novel findings, thus enhancing the understanding of AD pathophysiology and potential diagnostic avenues (ref: Ali doi.org/10.1016/j.neuron.2025.02.014/). Furthermore, the comparative efficacy of plasma p-tau217 and tau-PET in predicting cognitive decline among cognitively unimpaired individuals was explored, revealing similar associations with cognitive decline, which underscores the importance of these biomarkers in clinical trials (ref: Ossenkoppele doi.org/10.1038/s43587-025-00835-z/). The potential for biofluid-based staging of AD was also examined, indicating that biomarkers like p-tau217 could effectively categorize disease stages, thus aiding in clinical decision-making (ref: Lantero-Rodriguez doi.org/10.1007/s00401-025-02863-w/). Lastly, a systematic review of neuroinflammatory biomarkers in AD highlighted the need for more longitudinal studies to validate these findings for clinical application (ref: Heneka doi.org/10.1038/s41380-025-02939-9/).

The exploration of therapeutic interventions for Alzheimer's disease (AD) has yielded varied results across recent clinical trials. A phase 2a trial assessed the safety and efficacy of laromestrocel, an allogeneic mesenchymal stem cell therapy, in mild AD patients. The study, which involved multiple infusion groups, aimed to evaluate the therapy's impact on clinical progression and neuroinflammation, but the results on efficacy remain inconclusive (ref: Rash doi.org/10.1038/s41591-025-03559-0/). In contrast, a phase 3 trial of escitalopram for treating agitation in AD found that it was not effective and raised concerns about cardiac risks, highlighting the complexities of pharmacological interventions in this population (ref: Rajji doi.org/10.1038/s41591-025-03569-y/). Additionally, the open-label extension of the DIAN-TU trial for gantenerumab treatment in dominantly inherited AD revealed early termination due to lack of regulatory approval, emphasizing the challenges faced in developing effective therapies (ref: Bateman doi.org/10.1016/S1474-4422(25)00024-9/). A systematic review and meta-analysis of passive immunotherapies targeting amyloid beta indicated potential efficacy but also raised safety concerns, suggesting that while these therapies may offer new avenues for treatment, their clinical application requires careful consideration (ref: Tonegawa-Kuji doi.org/10.1371/journal.pmed.1004568/). Lastly, innovative approaches using cerebrospinal fluid metabolomics have begun to uncover biological mechanisms underlying AD, providing a foundation for future therapeutic strategies (ref: Reus doi.org/10.1038/s41380-025-02934-0/).

Neuroinflammation plays a crucial role in the pathology of Alzheimer's disease (AD), with recent studies elucidating the mechanisms involved. One study demonstrated that interleukin-12 signaling disrupts neuronal and oligodendrocyte homeostasis, contributing to AD pathology. The inhibition of this signaling pathway in AD-like mouse models showed promise in attenuating disease progression, suggesting that targeting neuroinflammatory pathways may offer therapeutic benefits (ref: Schneeberger doi.org/10.1038/s43587-025-00816-2/). Additionally, research into tau filaments revealed structural insights into the Alzheimer fold in human MAPT mutants, providing a deeper understanding of tau pathology and its implications for neurodegeneration (ref: Qi doi.org/10.1038/s41594-025-01498-5/). The exploration of cellular metabolism in neurodegenerative diseases has also gained traction, with studies indicating that alterations in energy metabolism, as evidenced by simultaneous monitoring of tyrosinase and ATP levels in AD mouse models, correlate with disease progression (ref: Huang doi.org/10.1002/advs.202413220/). Furthermore, the investigation of α-synuclein co-pathology in AD has highlighted its potential role in exacerbating tau aggregation, suggesting that co-pathologies may significantly influence disease trajectories and cognitive decline (ref: Franzmeier doi.org/10.1186/s13024-025-00822-3/). Collectively, these findings underscore the intricate interplay between neuroinflammation, tau pathology, and metabolic dysregulation in AD.

Genetic factors play a pivotal role in the susceptibility and resilience to Alzheimer's disease (AD), with recent studies shedding light on the underlying molecular mechanisms. The APOE genotype has been identified as a significant risk factor, with APOE4 carriers exhibiting distinct pathological features compared to APOE3 and APOE2 carriers. Specifically, research found that excitatory neurons in APOE4 carriers displayed reduced synaptic pathways, while oligodendrocytes showed increased myelination pathways, indicating a complex interaction between genetic risk and cellular responses (ref: Li doi.org/10.1016/j.neuron.2025.02.017/). Additionally, long-read RNA sequencing has provided insights into the genetic regulation of microglial splicing, revealing disease-associated variants that may contribute to neurodegenerative processes (ref: Humphrey doi.org/10.1038/s41588-025-02099-0/). Structural variants linked to AD have also been investigated, with findings suggesting that these genomic rearrangements may elucidate functional mechanisms underlying genetic associations identified in genome-wide association studies (ref: Vialle doi.org/10.1186/s13073-025-01444-6/). Furthermore, novel modeling approaches have been developed to understand the genetic architecture of resilience in aging individuals who meet pathological criteria for AD but remain cognitively intact, highlighting the importance of genetic factors in protective mechanisms (ref: Phillips doi.org/10.1093/brain/). These studies collectively emphasize the multifaceted genetic landscape of AD and its implications for understanding disease mechanisms and developing targeted interventions.

The assessment of cognitive health in aging populations has increasingly leveraged technology to enhance detection and monitoring of cognitive impairment. A large-scale study utilizing consumer-grade mobile devices collected extensive longitudinal data from over 23,000 participants, demonstrating the feasibility of remote cognitive assessments through smartphones and smartwatches. This approach not only captures routine device usage but also integrates self-reported health information, providing a comprehensive view of cognitive health over time (ref: Butler doi.org/10.1038/s41591-024-03475-9/). Additionally, computational models have been employed to predict cognitive decline by analyzing the architecture of brain networks, revealing that memory capacities can serve as indicators of aging and cognitive deterioration (ref: Mijalkov doi.org/10.1038/s41467-025-57995-0/). The interplay between cognitive health and neurodegenerative processes has also been explored, with findings indicating that co-pathologies, such as α-synuclein aggregation, may accelerate tau accumulation in AD, further complicating cognitive assessments (ref: Franzmeier doi.org/10.1186/s13024-025-00822-3/). These advancements in cognitive assessment methodologies underscore the importance of integrating technology and innovative analytical approaches to enhance early detection and intervention strategies in aging populations.

Dietary patterns and lifestyle factors have emerged as critical components influencing the risk of developing Alzheimer's disease (AD) and promoting healthy aging. A recent study identified optimal dietary patterns, such as a healthful plant-based diet and the Alternative Healthy Eating Index, which were associated with significantly improved odds of healthy aging. Specifically, the Alternative Healthy Eating Index demonstrated the strongest association with healthy aging in individuals aged 75 and older, with an odds ratio of 2.24, indicating a robust link between diet and cognitive health (ref: Tessier doi.org/10.1038/s41591-025-03570-5/). Furthermore, a systematic review and meta-analysis explored the neuropathological connections between type 2 diabetes mellitus (T2DM) and late-onset Alzheimer's dementia (LOAD), revealing shared pathophysiological mechanisms that increase the risk of cognitive decline. The review highlighted 93 gene loci associated with these risk linkages, emphasizing the need for further research into the interplay between metabolic disorders and neurodegenerative diseases (ref: Lemche doi.org/10.1152/physrev.00040.2024/). These findings underscore the importance of dietary and lifestyle interventions as potential strategies for mitigating the risk of AD and promoting cognitive health in aging populations.

Technological advancements are revolutionizing Alzheimer's disease (AD) research, particularly in the realms of diagnostics and therapeutic development. The introduction of Spotiphy, a computational toolkit for spatial transcriptomics, allows researchers to visualize gene expression at single-cell resolution across whole tissue sections, enhancing the understanding of cellular heterogeneity in AD pathology (ref: Yang doi.org/10.1038/s41592-025-02622-5/). This innovation is critical for dissecting the complex interactions within the brain's microenvironment and identifying potential therapeutic targets. Additionally, the application of cerebrospinal fluid metabolomics has provided insights into the biological mechanisms underlying AD, paving the way for novel therapeutic strategies (ref: Reus doi.org/10.1038/s41380-025-02934-0/). Furthermore, the integration of advanced imaging techniques and computational models has facilitated the exploration of neuroinflammatory pathways and their contributions to neurodegeneration, highlighting the potential for targeted interventions (ref: Schneeberger doi.org/10.1038/s43587-025-00816-2/). These technological innovations not only enhance the understanding of AD mechanisms but also hold promise for improving diagnostic accuracy and developing effective treatments.

Research into sex differences in Alzheimer's disease (AD) has revealed significant disparities in disease progression and pathology. A meta-analysis examining longitudinal tau-PET data found that female sex was associated with faster tau accumulation in individuals with high baseline amyloid-beta levels, particularly in regions such as the inferior temporal and lateral occipital areas. This suggests that biological sex may influence the trajectory of tau pathology in AD, with females potentially experiencing more rapid neurodegeneration (ref: Coughlan doi.org/10.1001/jamaneurol.2025.0013/). Additionally, the interplay between sex and genetic factors, such as APOE4 carrier status, further complicates the understanding of AD pathology, indicating that sex-specific mechanisms may underlie the differential risk and progression of the disease. These findings underscore the importance of considering sex differences in both research and clinical practice to tailor interventions and improve outcomes for individuals affected by AD (ref: Coughlan doi.org/10.1001/jamaneurol.2025.0013/).