Journal of Alzheimer's Disease最新文献

{"title":"Moderate coffee and tea consumption is associated with slower cognitive decline.","authors":"Stephanie R Rainey-Smith, Kelsey R Sewell, Belinda M Brown, Hamid R Sohrabi, Ralph N Martins, Samantha L Gardener","doi":"10.1177/13872877251361058","DOIUrl":"https://doi.org/10.1177/13872877251361058","url":null,"abstract":"<p><p>BackgroundGlobally, coffee and tea are consumed extensively, potentially providing neuroprotection through anti-inflammatory and antioxidative stress effects.ObjectiveThis study aimed to investigate associations between coffee and tea intake and cognitive function.MethodsIn a longitudinal prospective cohort study, dementia-free (<i>n</i> = 8715; age range 60.0-85.2 years) older adults from the UK Biobank self-reported coffee and tea intake over the previous year; 'never', 'moderate' (1-3 cups/day), or 'high' (≥4 cups/day). Participants completed cognitive assessments at ≥2 timepoints (mean of 9.11 years).ResultsThose 'never' consuming coffee and 'moderate' coffee consumers (<i>β</i> = 0.06, <i>p</i> = 0.005; <i>β</i> = 0.07, <i>p</i> < 0.001, respectively), as well as 'moderate' tea consumers and 'high' tea consumers (<i>β</i> = 0.06, <i>p</i> = 0.009; <i>β</i> = 0.06, <i>p</i> = 0.003, respectively) had slower fluid intelligence decline. Additionally, those 'never' consuming coffee and 'moderate' coffee consumers had a slower increase in pairs matching errors (β = -0.05, <i>p</i> = 0.022; β = 0.05, <i>p</i> = 0.013) compared to 'high' consumers.Conclusions<b>'</b>Moderate' coffee, and 'moderate' and 'high' tea intake may be a protective factor against cognitive decline. Randomized controlled trials are required to establish causal relationships leading to evidence-based recommendations regarding benefits of coffee and tea intake.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251361058"},"PeriodicalIF":3.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preliminary longitudinal epigenetic clock analyses of patients with mild cognitive impairment through nutritional intervention.","authors":"Kiriko Minami, Toshiyuki Shirai, Satoshi Okazaki, Shohei Okada, Masao Miyachi, Ikuo Otsuka, Akitoyo Hishimoto","doi":"10.1177/13872877251360230","DOIUrl":"https://doi.org/10.1177/13872877251360230","url":null,"abstract":"<p><p>BackgroundMild cognitive impairment (MCI) is an intermediate stage between normal aging and dementia. Not a small number of patients with MCI progress to Alzheimer's disease within 1 year. Epigenetic changes in DNA methylation, such as those observed in the epigenetic clock, are receiving increasing attention in the field of aging research. It is crucial to demonstrate the effectiveness of interventions for patients with MCI from a biological perspective to promote the prevention of dementia.ObjectiveWe conducted epigenetic clock analysis, mainly longitudinal evaluation, on patients with MCI who received intervention with vitamin D and/or marine omega-3 fatty acid supplements.MethodsWe conducted epigenetic clock analyses with public DNA methylation datasets from the Gene Expression Omnibus database. This dataset contains two timepoints' longitudinal DNA methylation data of 25 patients with MCI and 20 controls. They received two-year intervention with vitamin D and/or marine omega-3 fatty acid supplements. We conducted comparative analyses with Wilcoxon signed-rank test, and regression analyses of three models.ResultsIn patients with MCI, PhenoAge and GrimAge significantly decelerated after the intervention in comparative analyses. These clocks nominally significantly decelerated also in most of regression analyses. Moreover, natural killer cells showed significant differences before and after the intervention.ConclusionsWe found deceleration of some epigenetic clocks in patients with MCI with interventions. We believe that it is crucial to conduct additional epigenetic clock analyses in cohorts with larger sample sizes or in cohorts with interventions such as occupational therapy and pharmacotherapy are actively conducted.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251360230"},"PeriodicalIF":3.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preliminary study of sex-based neural responses and cognitive benefits of a 40 Hz rhythmic light intervention in mild cognitive impairment.","authors":"Ola A Alsalman, Weixin Li, Mariana G Figueiro","doi":"10.1177/13872877251361061","DOIUrl":"10.1177/13872877251361061","url":null,"abstract":"<p><p>BackgroundSex differences in the brain's structure, function, and response to interventions are increasingly recognized as critical factors in neurodegenerative diseases like mild cognitive impairment (MCI) and Alzheimer's disease.ObjectiveThis study investigated sex differences in brain activity among participants classified as having MCI (based on Montreal Cognitive Assessment scores) during exposure to a 40 Hz rhythmic light (RL) intervention versus a control RL condition.MethodsTwenty-four participants in the MCI group (mean age = 74.5 years, SD = 9.06; 15 women, 9 men) and 16 age-matched healthy controls (mean age = 70 years, SD = 8.97; 9 women, 7 men) were exposed to both light conditions and underwent electroencephalography recordings, cognitive performance testing (2-back task), and a subjective assessment of sleepiness (Karolinska Sleepiness Scale).Results40 Hz RL increased gamma power significantly, indicating its potential to enhance brain function, especially in the MCI group. Men showed greater neural response and better cognitive performance under the 40 Hz RL while women (particularly in the MCI group) responded more strongly to the control. The sleepiness results were not significant.ConclusionsThere is compelling evidence that 40 Hz RL has sex-dependent effects on gamma oscillations and cognitive performance, particularly in individuals with MCI. Men may benefit more directly from gamma-enhancing interventions, whereas women may require alternative approaches that account for their unique neural responses to light. Further research with larger, more diverse populations is needed to confirm these findings and explore the potential for personalized therapeutic strategies based on sex and cognitive status.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251361061"},"PeriodicalIF":3.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of diffusivity along the perivascular space in early- and late-onset Alzheimer's disease.","authors":"Xiao Luo, Hui Hong, Shuyue Wang, Kaicheng Li, Qingze Zeng, Xiaocao Liu, Luwei Hong, Jixuan Li, Xinyi Zhang, Siyan Zhong, Lingyun Liu, Chao Wang, Yanxing Chen, Minming Zhang, Peiyu Huang","doi":"10.1177/13872877251360416","DOIUrl":"https://doi.org/10.1177/13872877251360416","url":null,"abstract":"<p><p>BackgroundCerebrospinal fluid (CSF) dynamics plays a key role in clearing soluble amyloid-β from the brain, which may impact Alzheimer's disease (AD) onset.ObjectiveThis study seeks to differentiate cerebrospinal fluid dysfunction between early-onset AD (EOAD) and late-onset AD (LOAD) subtypes and to examine their associations with brain changes and cognitive function.MethodsWe performed in vivo imaging measurements on 40 EOAD patients, 38 LOAD patients, 69 age-matched young normal controls (YNC), and 60 old normal controls (ONC). Measured variables included diffusion tensor imaging along the perivascular space (DTI-ALPS, subdivided into left, right, and mean), amyloid and tau PET standardized uptake value ratios (SUVR), hippocampus volume, and white matter hyperintensities (WMH) volume. For normally distributed variables, we used ANOVA to assess group differences, followed by Tukey's HSD test for multiple comparison correction. Results without correction are marked. Pearson correlation and linear regression analyzed relationships between the DTI-ALPS index, brain parameters, and cognition within each subgroup.ResultsBoth EOAD (p < 0.05, uncorrected) and LOAD (p < 0.05, corrected) showed a lower DTI-ALPS index compared to controls. This lower index was associated with increased disease severity and worsening cognitive performance. In EOAD, the lower DTI-ALPS index was primarily linked to amyloid (Std beta = -0.463, p = 0.008), while in LOAD, it was predominantly associated with age (Std beta = -0.348, p = 0.006) and WMH (Std beta = -0.330, p = 0.009).ConclusionsThis observation suggests that differences in the etiology of cerebrospinal fluid dysfunction may exist between these AD subtypes, warranting further investigation to confirm these hypotheses.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251360416"},"PeriodicalIF":3.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global and regional white matter hyperintensities in Alzheimer's disease: Exploring etiologies and cognitive correlates.","authors":"Yuyue Qiu, Jialu Bao, Tianyi Wang, Li Shang, Shanshan Chu, Wei Jin, Wenjun Wang, Yuhan Jiang, Bo Li, Yixuan Huang, Bo Hou, Longze Sha, Yunfan You, Yuanheng Li, Ling Qiu, Qi Xu, Feng Feng, Liling Dong, Chenhui Mao, Jing Gao","doi":"10.1177/13872877251360239","DOIUrl":"https://doi.org/10.1177/13872877251360239","url":null,"abstract":"<p><p>BackgroundWhite matter hyperintensities (WMH) are commonly observed in Alzheimer's disease (AD), but their underlying pathophysiology remains poorly understood.ObjectiveThis cross-sectional study aims to explore the multifactorial etiologies and cognitive correlates of global and regional WMH in a cohort of biologically diagnosed AD patients.MethodsWe included 170 AD patients who underwent brain MRI, neuropsychological testing, and cerebrospinal fluid (CSF) biomarker evaluation within three months. Linear and logostic regressions were used to assess associations between global/regional WMH and age, cerebral microbleeds (CMB), AD biomarkers, cortical atrophy, and vascular risk scores. Sensitivity analyses included replacing vascular score with hypertension, p-tau181 with t-tau, and inclusion of <i>APOE</i> ε4 status. Associations between Mini-Mental State Exam scores and WMH and atrophy burden were also evaluated, adjusting for age, sex, and education.ResultsGreater global WMH burden was significantly associated with older age (β = 0.03, p < 0.001), lower CSF Aβ₄₂ levels (β = -0.0014, p = 0.01), and more severe CMB grade (β = 0.48, p = 0.003), but not with vascular risk scores. Regionally, WMH in the paraventricular, frontal, and parietal lobes were linked to CSF Aβ₄₂ and CMB. Cognitive impairment was independently associated with increased paraventricular WMH burden (β = -0.22, p < 0.001) and medial temporal atrophy (β = -0.82, p < 0.001).ConclusionsOur findings suggest that WMH in AD-particularly in the paraventricular, frontal, and parietal areas-are driven more by AD-specific pathology, including amyloid deposition and cerebral amyloid angiopathy, than by conventional vascular risk. Paraventricular WMH contribute to cognitive decline independent of cortical atrophy, underscoring their relevance as potential imaging biomarkers in AD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251360239"},"PeriodicalIF":3.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The global, regional, and national burden and attributable risk factors of Alzheimer's disease and other dementias, 1990-2021: A systematic analysis for the Global Burden of Disease Study.","authors":"Mengfan Yin, Shuting Ding, Manli Zhao, Junling Liu, Weiqiang Su, Min Fu, Minghao Wu, Chenyu Ma, Xiaodong Sun, Yujia Kong","doi":"10.1177/13872877251360221","DOIUrl":"https://doi.org/10.1177/13872877251360221","url":null,"abstract":"<p><p>BackgroundDementia is a syndrome characterized by a decline in cognitive function, with Alzheimer's disease (AD) being the most common type. Updated global statistics on the burden of AD and other dementias provide critical insights for guiding prevention and treatment strategies.ObjectiveTo estimate the global, regional, and national burden and attributable risk factors of AD and other dementias from 1990 to 2021.MethodsThis cross-sectional study utilized the 2021 Global Burden of Disease (GBD) dataset from 204 countries and territories. The analysis focused on individuals aged 40 years and older with AD and other dementias and included data on incidence, all-cause and cause-specific mortality, disability-adjusted life years (DALYs), and estimated annual percentage changes (EAPCs). These trends were stratified by region, country, age, sex, and Socio-Demographic Index (SDI).ResultsFrom 1990 to 2021, global DALYs attributable to AD and other dementias rose from 3.83 million to 9.84 million. Age-standardized rates (ASRs) of incidence and DALYs increased for both sexes, with a more pronounced rise in males. ASRs for incidence, prevalence, and DALYs were positively correlated with SDI. Smoking was identified as the primary risk factor for dementia burden among males, whereas obesity was the leading risk factor for females.ConclusionsThe global burden of AD and other dementias has significantly increased from 1990 to 2021, especially in high-SDI regions. While females have a higher overall risk, the burden has grown more rapidly in males. These findings highlight the need for targeted interventions to address aging populations and reduce dementia risk factors.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251360221"},"PeriodicalIF":3.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting diagnostic conversion from mild cognitive impairment to Alzheimer's disease: A Bayesian hierarchical model approach using ADNI patient data.","authors":"Hugo Senra, Maria Conceição Costa, Isabel Pereira, Daniel Agostinho, Miguel Castelo-Branco","doi":"10.1177/13872877251360228","DOIUrl":"https://doi.org/10.1177/13872877251360228","url":null,"abstract":"<p><p>BackgroundThere is still need for a better understanding of which specific follow-up medical assessments might offer greater predictive value for diagnostic conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD).ObjectiveTo examine the longitudinal predictive importance of follow-up medical assessments to detect diagnostic conversion from MCI to AD.MethodsA sample of 572 participants from the ADNI database with valid data at baseline medical visit were included. Bayesian hierarchical models were employed to investigate longitudinal predictors of diagnostic conversion in a 36-month medical follow-up cohort, for measures of cognitive function, psychopathological symptoms, and demographical data. An additional 48-month medical follow-up cohort was considered to investigate the predictive importance of cerebrospinal fluid biomarkers (Aβ₄₂/Aβ₄₀ ratio) for diagnostic conversion.ResultsMini-mental State Examination (MMSE) (β = -2.6; 95% HDI: [-3.6--1.5]) and Clinical Dementia Rating scale Sum of Boxes (CDR-SB) (β = 5.6; 95% HDI: [4.3-7.0]) can predict diagnostic conversion from MCI to AD over a 36-month medical follow-up, with CDR-SB showing the greatest predictive importance in all Bayesian models. Higher scores on CDR-SB were associated with increased risk for a diagnosis conversion, approximately 30% greater probability at 24-month follow-up, and > 50% greater probability at 36-month follow-up.ConclusionsThe CDR-SB provides a reliable cognitive assessment to detect diagnostic conversion from MCI to AD over a period of 36 months, which is key to help clinicians screening for early diagnosis of AD using affordable non-invasive procedures.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251360228"},"PeriodicalIF":3.4,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reducing falls in inpatient older adults: Quality improvement initiative.","authors":"Munira Sultana, Catherine Taylor, Danica McPhee, Antoinette Chandler, Huzafa Hyde, Iman Yekinni, Nahiyan Sayeed, Matt Bessey","doi":"10.1177/13872877251360031","DOIUrl":"https://doi.org/10.1177/13872877251360031","url":null,"abstract":"<p><p>BackgroundFalls and fall-related injuries are common among older adults, adversely affecting their functional independence and quality of life. By 2043, one in three Canadians falls each year, resulting in 85% of hospitalizations, which cost $2 billion annually.ObjectiveThis study aimed to reduce inpatient falls among older adults with cognitive impairment in a rural Ontario hospital.MethodsA fall reduction project was implemented at the hospital to improve clinical care since January 2024. The project included fall risk screening, ensuring a fall bundle was in place, and monthly meetings with hospital staff and patient representatives to identify potential barriers and facilitators to the project. The project involved two components: 1) nurses evaluating fall risk using validated tools and 2) implementing a fall prevention bundle. Data was retrieved from the hospital's electronic medical records. The outcome of interest was the fall rate before and after the intervention.ResultsThe initiative has reduced the inpatient fall rate from 16.25 falls per 1000 bed days in 2023 to 11.33 falls per 1000 bed days in 2024. Almost 57% of people who fell were cognitively impaired.ConclusionsThe project reduced the inpatient fall rate by 30% within a year. The involvement of patients and their families in the initiative has made the project meaningful to the community. However, no change was observed in the 30-day readmission rate, prompting the research team to conclude that inpatient interventions are insufficient. Further research on collaborative care involving the pharmacy department and community partners is recommended.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251360031"},"PeriodicalIF":3.4,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alternative splicing in Alzheimer's disease: Mechanisms, therapeutic implications, and 3D modeling approaches.","authors":"Matthew Pasteris, Senem Cakir, Anna Bellizzi, Ilker K Sariyer","doi":"10.1177/13872877251359633","DOIUrl":"https://doi.org/10.1177/13872877251359633","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is characterized by progressive cognitive decline, memory loss, and behavioral changes. AD is pathologically marked by the accumulation of extracellular amyloid-β (Aβ) oligomers, amyloidogenic plaques, and intracellular neurofibrillary tangles. Amyloid-β protein precursor (AβPP) plays a central role in AD pathology, as it is cleaved by β-secretase and γ-secretase enzymes to generate Aβ peptides and oligomers which aggregate to form neurotoxic fibrils and plaques in the brain. Increased AβPP expression has been correlated to Aβ suggesting a larger role for AβPP function potentially through AβPP isoforms. Alternative splicing (AS) of APP pre-mRNA has emerged as a key regulatory mechanism influencing AβPP function through the generation of distinct isoforms. Similarly, the microtubule-associated protein tau (MAPT) is also subject to alternative splicing, producing isoforms that can contribute to hyperphosphorylation and neurodegeneration. In this review, we explore the role of APP alternative splicing and the regulation of its isoform expression in AD and other neurodegenerative disorders, with a focus on its potential impact on Aβ peptide production. We also discuss recent advances in therapies targeting dysregulated splicing in neurodegenerative diseases and their potential relevance to AD. Finally, we highlight the use of three-dimensional culture models as a platform to study AS regulation in AD and other neurodegeneration-related disorders.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251359633"},"PeriodicalIF":3.4,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of machine learning reveals diagnostic biomarkers related to pyroptosis in Alzheimer's disease and analysis of immune infiltration.","authors":"Yujuan Huang, Tu Xu, Li Wang, Ruping Xiang, Meijun Zhou, Huiyun Yu, Dong Liu, Zhicheng Chen","doi":"10.1177/13872877251360033","DOIUrl":"https://doi.org/10.1177/13872877251360033","url":null,"abstract":"<p><p>BackgroundAlzheimer's disease (AD) is characterized by complex pathological mechanisms, with pyroptosis potentially contributing to neuroinflammation.ObjectiveTo identify pyroptosis-related genes (PRGs) in AD and explore their role in neuroinflammation, aiming to provide potential biomarkers and therapeutic targets for precision medicine in AD treatment.MethodsTranscriptomic data from AD brain tissues (GEO database) were analyzed using multi-omics integration and machine learning. Key PRGs were screened via weighted gene co-expression network analysis (WGCNA), LASSO regression, random forest, and SVM-RFE algorithms. Molecular subtypes and therapeutic potential were assessed through unsupervised clustering and molecular docking.ResultsAnalysis identified 609 differentially expressed genes (DEGs), with upregulated genes enriched in DNA transcription and mitosis-related pathways. Six core PRGs (MIB1, TUG1, GATA1, CA1, CFH, IL17A) demonstrated strong diagnostic accuracy (AUC > 0.85). Unsupervised clustering revealed two AD subtypes: a high-risk subtype with activated pyroptosis-inflammatory pathways and distinct immune microenvironment features (p < 0.05). Molecular docking confirmed stable binding between CFH and the anti-AD drug candidate fludrocortisone (binding energy < -7 kcal/mol).ConclusionsPyroptosis modulates neuroinflammation to drive AD progression. CFH and other PRGs serve as promising biomarkers and therapeutic targets, advancing precision strategies for AD subtyping and intervention.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251360033"},"PeriodicalIF":3.4,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}