Background Amnestic mild cognitive impairment (aMCI) is considered a prodromal phase of Alzheimer’s disease (AD). However, little is known about the neuropsychological characteristic at pre-MCI stage. This study aimed to investigate which neuropsychological tests could significantly predict aMCI from a seven-year longitudinal cohort study. Methods The present study included 123 individuals with baseline cognitive normal (NC) diagnosis and a 7-year follow-up visit. All the subjects were from the China Longitudinal Aging Study (CLAS) study. Participants were divided into two groups, non-converter and converter based on whether progression to aMCI at follow-up. All participants underwent standardized comprehensive neuropsychological tests, including the mini-mental state examination (MMSE), Montreal Cognitive Assessment (MoCA), auditory verbal learning test (AVLT), the digital span test, the verbal fluency test, the visual recognition test, the WAIS picture completion task, and WAIS block design. Logistic regression analysis was used to evaluate the predictive power of baseline cognitive performance for the transformation of amnestic mild cognitive impairment. Receiver operating characteristic (ROC) curve was used to test the most sensitive test for distinguishing different groups. Results Between the non-converter group and converter group, there were significant differences in the baseline scores of AVLT-delayed recall (AVLT-DR) (8.70 ± 3.61 vs. 6.81 ± 2.96, p = 0.001) and WAIS block design (29.86 ± 7.07 vs. 26.53 ± 8.29, p = 0.041). After controlling for gender, age, and education level, converter group showed lower baseline AVLT-DR than non-converter group, while no significant difference was found in WAIS block design. Furthermore, converter group had lower AVLT-DR score after controlling for somatic disease. The area under the curve of regression equation model was 0.738 (95%CI:0.635–0.840), with a sensitivity 83.9%, specificity of 63.6%. Conclusions Our results proved the value of delayed recall of AVLT in predicting conversion to aMCI. Early and careful checking of the cognitive function among older people should be emphasized.

BACKGROUND:Ventricular tachycardia (VT) storm from the left ventricular outflow tract epicardium is challenging, especially after coronary artery bypass grafting and mechanical aortic valve replacement. CASE SUMMARY:A 68-year-old man with history of coronary artery bypass grafting, mechanical aortic valve replacement, hypertension, diabetes, and untreated chronic obstructive pulmonary disease presented with recurrent chest tightness, palpitations, syncope, and symptomatic wide QRS complex VT. He developed VT storm (>100 implantable cardioverter-defibrillator shocks/d). Trans-coronary sinus-great cardiac vein (CS-GCV) ablation (guided by three-dimensional mapping) succeeded; no postprocedural VT/premature ventricular contractions, with sustained efficacy on follow-up. DISCUSSION:This case demonstrates that CS-GCV ablation manages epicardial VT storm despite anatomical challenges. Preprocedural imaging and intraoperative navigation are key; PTCA wire unipolar mapping optimizes targeting, reducing complications versus retrograde aortic access in post-valve surgery patients. TAKE-HOME MESSAGES:Epicardial VT storm can be managed via CS-GCV ablation despite anatomical challenges. Preprocedural imaging/intraoperative navigation ensure success; PTCA wire mapping optimizes targeting, and intracardiac echocardiography ensures safety. It is safer than retrograde aortic access for post-valve surgery patients.

BackgroundIn patients with heart failure with preserved ejection fraction (HFpEF), further investigation of the safety and long-term efficacy of combined radiofrequency catheter ablation and left atrial appendage closure (RF + LAAC) in patients with HFpEF is warranted.MethodsIn this retrospective study, we aimed to evaluate the outcome of RF + LAAC in patients with AF and HFpEF, compared to radiofrequency catheter ablation (RF) alone. 331 patients with AF and chronic HFpEF were divided into two groups: RF + LAAC (n = 196) and RF (n = 135). After 1:1 propensity score matching (PSM), 96 matched pairs were enrolled in further analysis. HF rehospitalization, ischemic stroke/transient ischemic attack (TIA), and major bleeding events were assessed over 24 months. Kaplan–Meier analyses were used to compare outcomes.ResultsThe RF + LAAC group demonstrated comparable procedural complication rates to RF alone (5.2% vs. 4.2%, p = 0.733). The risks of ischemic stroke/TIA (ARR=4.95%, HR = 0.096, 95%CI:0.012–0.753, p = 0.026) and major bleeding events (ARR=3.91%, HR = 0.120, 95%CI: 0.015–0.957, p = 0.045) were significantly lower in RF + LAAC group vs. RF alone, while HF rehospitalization was similar between the two groups (ARR=−0.56%, HR = 1.356, 95%CI: 0.303–6.059, p = 0.690).ConclusionsIn patients with AF and HFpEF, combined RF + LAAC was associated with lower risks of ischemic stroke/TIA and major bleeding, without an observed increase in HF rehospitalization, compared with RF alone.

Background and Aim(s): Metabolic dysfunction-associated steatotic liver disease (MASLD) lacks reliable early biomarkers. This study aimed to investigate the prognostic value of serum scEMC10 and establish a predictive model for MASLD. Methods: A 4.6-year prospective cohort study of 769 initially MASLD-free Chinese adults were conducted. Serum scEMC10 levels were measured via ELISA. Multivariable logistic regression identified independent predictors to develop the MASLD-scEMC10 model, which was compared against established indices using ROC-AUC analysis. Results: Baseline scEMC10 levels were significantly higher in participants who developed MASLD (4.60 vs. 2.55 ng/mL, P<0.001). scEMC10 was an independent predictor (OR=1.05, P<0.001). The MASLD-scEMC10 model (BMI, HbA1c, adiponectin, scEMC10) demonstrated superior predictive accuracy (AUC=0.8142, 95% CI: 0.758–0.870) compared to scEMC10 alone (AUC=0.6531, P<0.01) and other established indices like FLI, HIS, and ZJU. Conclusions: Serum scEMC10 is a significant independent predictor of MASLD. The proposed MASLD-scEMC10 model provides excellent predictive accuracy, suggesting an etiological role for scEMC10 in MASLD and offering a valuable tool for early clinical risk stratification.

This prospective birth cohort study, conducted in China with 21 893 singleton pregnant women, aimed to investigate the association between metabolic obesity phenotypes and the risks of gestational hypertension (GH) and preeclampsia (PE), as well as to explore the potential interaction between obesity and metabolic abnormalities in relation to these conditions. Participants were categorized according to their pre-pregnancy BMI and metabolic status into different obesity metabolic phenotypes. The diagnosis of GH and PE was based on blood pressure measurements, evidence of end-organ dysfunction, or proteinuria occurring after 20 weeks of gestation. The results indicated that, compared to metabolically healthy normal-weight women, those with metabolically unhealthy normal weight, metabolically healthy overweight/obesity, and metabolically unhealthy overweight/obesity all had significantly elevated risks for both GH (with adjusted odds ratios ranging from 1.77 to 3.89) and PE (adjusted ORs from 1.58 to 4.51). In contrast, metabolically healthy underweight women were found to have a lower risk of GH. Furthermore, an additive interaction was observed between overweight and metabolic unhealthiness, which increased the risk of GH by 1.15 times, representing a 28% relative excess risk. The combined risk for women exposed to both factors was 1.58 times greater than the risk associated with either factor alone. In conclusion, both metabolic abnormalities and overweight/obesity elevate the risks of GH and PE, and a significant interaction effect exists between these two factors.

BACKGROUND:Women with a history of gestational diabetes mellitus (GDM) are at increased risk of developing type 2 diabetes later in life. This study evaluated whether lifestyle intervention can reduce the risk of type 2 diabetes in women with previous GDM. METHODS:This was a two-arm randomized controlled study conducted at the Tianjin Women and Children's Health Center. Women in six urban districts of Tianjin with previous GDM were randomly assigned in a 1: 1 ratio to either a 4-year lifestyle intervention group or a standard care control group between August 1, 2009 and July 31, 2011. Random allocation sequences were generated in patients but not in study coordinators. Each participant in the intervention group received individualized counseling aimed at reducing body weight in overweight women, increasing physical activity, and maintaining appropriate intakes of fat and carbohydrates especially fiber. Major components included six face-to-face meetings with a dietitian in the first year and two additional sessions in each subsequent year. The primary outcome was the development of type 2 diabetes, assessed using an oral glucose-tolerance test (OGTT). Participants were followed until the date of the diagnosis of diabetes, the last date of an OGTT, or death, whichever occurred first, up to December 2020. For participants who missed any OGTTs, self-reported physician-diagnosed diabetes data were collected. RESULTS:A total of 1180 women with a recent history of GDM were randomized to either an intensive lifestyle intervention ( n = 586) or usual care ( n = 594) 1-5 years postpartum (mean: 2.26 years). The mean follow-up was 4.5 years. During the trial, women in the intervention group, compared with the control group, lost more weight, increased physical activity and consumed more fiber. The incidence of diabetes after four years or more of follow-up was 9.0 and 15.3 cases per 1000 person-years in the lifestyle intervention and control groups, respectively. The lifestyle intervention reduced the incidence of diabetes by 46% (95% confidence interval: 10-67%) using the OGTT to diagnose diabetes, and by 40% (95% confidence interval: 11-59%) using either the OGTT or self-reported physician-diagnosed diabetes. CONCLUSIONS:Healthy lifestyle management significantly reduced the incidence of diabetes among young women with previous GDM. TRIAL REGISTRATION:ClinicalTrials.gov , NCT01554358.

Titanium alloys used in orthopedic implants suffer from wear-induced debris formation. Hydrogel coating modification is an effective strategy to address this challenge, but it fails to meet the requirements for surface lubrication and long-term stability of implants. This study proposes a dynamic self-healing hydrogel coating modification strategy based on Schiff base bonds, aiming to optimize the hydrogel network structure by regulating the solvent ratio and construct a high-performance hydrogel to improve the tribological properties of titanium alloy surfaces. A dual network of acrylamide and polyvinyl alcohol was formed simultaneously, and different ratios of dimethyl sulfoxide were introduced into the aqueous system to construct the hydrogel synergistically. The results showed that the friction coefficient of the Ti6Al4V alloy plate modified with the dual-network bio-lubricating hydrogel coating was only 0.051, decreased by 88.54

Abstract Objective Androgens are increasingly recognized as important regulators of metabolic balance and vascular integrity. However, their relationship with diabetic retinopathy (DR) remains incompletely defined and appears to differ by sex. The present study aimed to examine the associations between circulating levels of total testosterone (TT), dehydroepiandrosterone sulfate (DHEAS), and androstenedione (ASD) and DR risk among individuals with type 2 diabetes mellitus (T2DM), with particular emphasis on gender-stratified analyses. Methods This cross-sectional investigation analyzed 796 hospitalized T2DM cases. Serum concentrations of TT, DHEAS, and ASD were quantified using chemiluminescence immunoassays. Multivariable logistic regression was utilized to assess the associations between androgen levels and the presence of DR, with analyses conducted separately for men and women to account for sex-specific differences. Results Among male participants, after comprehensive adjustment for potential confounding variables, serum DHEAS levels were independently and inversely linked with DR risk (tertile 3 vs. tertile 1: OR = 0.43, 95% CI: 0.23–0.82; P for trend = 0.007). Restricted cubic spline modeling demonstrated an approximately linear inverse dose-response relationship between DHEAS concentrations and DR risk (overall P < 0.001; nonlinear P = 0.193). No correlations were found between serum TT or ASD levels and DR in men. In female patients, an inverse relationship between TT and DR was attenuated and rendered nonsignificant after full multivariable adjustment, and neither DHEAS nor ASD showed a statistically significant association with DR risk. Conclusions Lower serum DHEAS concentrations are independently linked with elevated DR risk in males with T2DM, suggesting a potential role for DHEAS in the pathophysiology of DR in males.

Women with a history of gestational diabetes mellitus (GDM) have a substantial 20–50

The roles of Contactin-2 (CNTN2) and ferroptosis in heart failure and cardiac remodeling remain incompletely understood. CNTN2 was significantly upregulated in hypertrophic cardiomyopathy patients and heart failure mice. In cardiomyocyte specific CNTN2 conditional knockout (CNTN2 cKO) mice, transverse aortic constriction (TAC) induced markedly exacerbated heart failure, cardiac remodeling and ferroptosis compared to control mice. Ferroptosis inhibition substantially attenuated heart failure in CNTN2 cKO mice subjected to TAC, indicating that enhanced ferroptosis contributes to the detrimental effects of CNTN2 deficiency. RNA sequencing identified NUPR1, a ferroptosis repressor, as a downstream molecule of CNTN2. Mechanistically, CNTN2 activated the Lyn/eIF2α/ATF4 pathway to regulate NUPR1. CNTN2 overexpression attenuated Angiotensin II-induced cardiomyocyte ferroptosis and pathological remodeling, whereas these protective effects were abolished by Lyn or NUPR1 inhibitors. We further revealed CNTN2 and Lyn interacted with each other, and that CNTN2 interacted with Lyn through its 1-328aa domain. In vivo NUPR1 overexpression via AAV9 significantly mitigated TAC-induced heart failure and cardiac remodeling in CNTN2 cKO mice. Our study demonstrates that CNTN2 protects against pressure overload induced heart failure and cardiac remodeling by regulating ferroptosis through the Lyn/eIF2α/ATF4/NUPR1 pathway, suggesting CNTN2 as a potential therapeutic target.

BACKGROUND:Left atrial appendage (LAA) patency after catheter ablation and LAA closure (LAAC) is a key determinant of postprocedure stroke. The effect of LAA electrical isolation (LAAEI) on LAA patency after LAAC in patients with atrial fibrillation (AF) remains unknown. Our objective was to explore the effect of LAAEI on LAA patency after catheter ablation and LAAC in patients with AF. METHODS:Patients with persistent AF who underwent combined catheter ablation and LAAC were enrolled. LAA patency was detected by cardiac computed tomographic angiography at 3 months after the procedure. RESULTS:A total of 686 patients with persistent AF with 3-month device surveillance by cardiac computed tomographic angiography were included initially. Propensity score matching analysis was conducted on the basis of clinical features, echocardiographic parameters and procedural characteristics, and 469 patients were matched, including 363 with non-LAAEI and 106 with LAAEI. Patients in matched groups showed 53.7% complete closure (no patency). Of the 46.3% of cases with LAA patency, visible peridevice leak was seen in 72.8%, and 27.2% had patency without visible peridevice leak. Compared with the non-LAAEI group, the LAAEI group had a lower rate of LAA patency (49.6% versus 34.9%; adjusted odds ratio, 0.69 [95% CI, 0.48-0.98]; P=0.040). LAAEI was protective against LAA patency with an odds ratio of 0.68, and the other predictor of contrast leak into the LAA was maximum diameter of LAA orifice (odds ratio, 1.04 [95% CI, 1.00-1.08]; P=0.046). CONCLUSIONS:LAAEI is an effective strategy for reducing LAA patency in patients with persistent AF undergoing combined catheter ablation and LAAC. REGISTRATION:URL: clinicaltrials.gov; Unique Identifier: NCT03788941.

Background:Gestational diabetes mellitus (GDM) induces progressive placental structural and functional abnormalities that are often undetectable by conventional ultrasound. Accurately assessing these changes is crucial for preventing adverse perinatal outcomes. This study aimed to evaluate the diagnostic value of multimodal ultrasound in assessing placental structural and functional alterations in pregnancies complicated by GDM, and to identify reliable sonographic biomarkers for evaluating placental abnormalities and clinical risk stratification. Methods:In this prospective study, 177 pregnant women undergoing routine antenatal care between 28 and 40 weeks of gestation were enrolled at Xiangyang No. 1 People's Hospital from September 2022 to December 2024, including 82 patients with GDM and 95 healthy controls. Multimodal ultrasound was performed using spectral Doppler, three-dimensional (3D) power Doppler imaging, and shear wave elastography (SWE) to assess uterine artery (UtA), umbilical artery (UA), and middle cerebral artery (MCA) hemodynamics, placental perfusion indices [vascularization index (VI), flow index (FI), vascularization flow index (VFI)], and placental stiffness [central and marginal mean elasticity (Emean)]. Postnatal placental vascular casting was conducted for supporting qualitative evidence. Group comparisons used independent t-tests or Mann-Whitney U tests as appropriate. Univariate and multivariate logistic regression and receiver operating characteristic (ROC) analyses (Youden index) were performed. Results:Compared with controls, the GDM group had higher pre-pregnancy body mass index (BMI) (22.21±2.11 vs. 20.84±1.79 kg/m2) and glycated hemoglobin (HbA1c) (5.78%±0.87% vs. 5.17%±0.73%), both P<0.001. UtA indices were elevated in GDM [pulsatility index (PI): 0.86±0.29 vs. 0.76±0.24, P=0.013; resistance index (RI): 0.52±0.08 vs. 0.49±0.07, P=0.009; systolic/diastolic ratio (S/D): 2.44±0.45 vs. 2.30±0.40, P=0.029]. Placental perfusion indices were reduced (VI: 32.10±5.81 vs. 34.02±6.13, P=0.036; FI: 55.30±4.47 vs. 57.10±4.92, P=0.012; VFI: 11.47±2.72 vs. 13.91±3.03, P=0.013), whereas placental stiffness increased (central Emean: 6.17±0.19 vs. 6.04±0.16 kPa, P<0.001; marginal Emean: 8.10±0.20 vs. 8.02±0.18 kPa, P=0.006). In multivariate analysis, VFI [odds ratio (OR) =0.84, P=0.035], central Emean (OR =1.18, P=0.015), and marginal Emean (OR =1.22, P=0.012) were independently associated with GDM. Diagnostic performance was high for VFI [area under the curve (AUC) =0.849], central Emean (AUC =0.859), and marginal Emean (AUC =0.845); their combined model achieved AUC =0.898 with 80.00% sensitivity and 89.58% specificity (P<0.0001). Conclusions:Multimodal ultrasound is a valuable noninvasive tool for detecting placental functional and structural abnormalities in GDM. Parameters such as VFI and placental elasticity may serve as effective biomarkers for monitoring GDM-related placental changes and prenatal management. Integration of these imaging modalities can enhance the precision of risk assessment and support individualized perinatal care.

OBJECTIVES:This study elucidated the cell-type-specific mechanisms and molecular targets underlying the anti-fibrotic effects of Abelmoschus manihot (AM) extract in diabetic kidney disease (DKD). We focused on identifying fibrosis-associated regulators using single-nucleus RNA sequencing (snRNA-seq) and validating them experimentally. METHODS:DKD was induced in C57BL/6J mice by a high-fat diet and streptozotocin. Mice received oral AM extract (2.0 g/kg/day) for 14 weeks. We performed snRNA-seq on control, DKD, and AM-treated kidneys, utilizing computational tools to infer intercellular communication. Validation was conducted using quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry, western blotting, and confocal microscopy. In vitro, human renal proximal tubular epithelial (HK-2) cells were exposed to high glucose (HG) with or without AM treatment. RESULTS:AM significantly reduced the urinary albumin-to-creatinine ratio and ameliorated glomerular and interstitial fibrosis in DKD mice. snRNA-seq identified proximal tubular segment 1 and interstitial cell clusters as the primary responders to AM. The extract suppressed transforming growth factor-beta TGF-β/Smad-related profibrotic signaling and remodeled epithelial-stromal intercellular communication by downregulating C-X-C motif chemokine ligand (CXCL) and colony-stimulating factor (CSF) pathways. Notably, spondin 1 (SPON1), an extracellular matrix-associated matricellular protein, was among the most significantly downregulated genes. Consistent with these findings, SPON1 expression was markedly reduced in both DKD kidneys and HG-injured HK-2 cells following AM administration. CONCLUSIONS:AM attenuates diabetic renal fibrosis by reducing SPON1 expression, suppressing profibrotic signaling, and remodeling epithelial-stromal crosstalk. These findings provide cell-type-resolved insights into AM's renoprotective mechanisms and highlight SPON1 as a candidate molecular target in DKD.

Early Alzheimer’s disease (AD) is increasingly understood as a phase in which neural circuit dysfunction emerges alongside molecular pathology and local neuronal injury. Although physical exercise has been linked to a deceleration in cognitive decline and beneficial cognitive and neural outcomes, most mechanistic explanations have predominantly focused on molecular or cellular pathways, with less emphasis on circuit-level interpretations. This narrative review integrates evidence from four neural systems that exhibit early vulnerability in AD and are pertinent to exercise-responsive cognitive or behavioral domains: the entorhinal cortex–dentate gyrus (EC–DG) circuit, the ventral hippocampus–medial prefrontal cortex (vHPC–mPFC) pathway, the medial septum/vertical diagonal band–hippocampal (MS/VDB–hippocampal) cholinergic circuit, and the suprachiasmatic nucleus–paraventricular nucleus (SCN–PVN) circadian axis. Across these systems, the evidence remains inconsistent. Direct circuit-level findings, including electrophysiological and functional-connectivity measurements, indicate circuit disruption in specific domains, whereas many exercise-related effects are inferred from molecular, structural, neurochemical, behavioral, or clinical-proxy outcomes. We therefore propose a multicircuit framework in which exercise may ameliorate AD-related cognitive and behavioral dysfunction through convergent but circuit-specific routes: EC–DG excitability and plasticity, vHPC–mPFC communication substrates, MS/VDB–hippocampal cholinergic modulation, and SCN–PVN circadian-neuroendocrine timing. This framework clarifies the evidence boundaries of exercise-related circuit modulation in early AD and identifies direct circuit-level measurements as a priority for future translational studies.

This paper estimates the causal effect of online food delivery platforms on body weight in China. Exploiting the staggered rollout of Eleme across Chinese cities between 2010 and 2020, we find that platform entry shifts the BMI distribution rightward among urban young adults: it increases body mass index, lowers underweight prevalence, and raises the likelihood of being overweight. Effects are negligible among urban older adults, consistent with lower platform adoption in this group. Mechanism analysis points to shifts in dietary preferences toward energy-dense foods, reduced meal preparation time, and increased restaurant entry. Our findings highlight the health trade-offs associated with digital food platforms in rapidly urbanizing developing countries, where improved caloric access may coexist with greater exposure to lower-quality, energy-dense foods.

OBJECTIVE: To determine the prevalence of different pain mechanisms, including nociplastic pain, and to evaluate the associations of these mechanisms with pain intensity, disability, pain catastrophizing, and quality of life in patients with chronic pain after total knee arthroplasty (TKA).MATERIALS and METHODS: This single-center cross-sectional observational study included 200 consecutive patients with chronic post-TKA pain between November 2022 and January 2023. Chronic post-TKA pain was defined as patient-reported pain in the operated knee persisting or recurring for more than three months after primary TKA, with a visual analog scale (VAS) score greater than 0 at the study visit. Neuropathic pain was identified using the painDETECT questionnaire. In patients not classified as possible or likely neuropathic pain, nociplastic pain affecting the musculoskeletal system was identified using the clinical criteria and grading system proposed by Kosek et al., including clinical history and bedside sensory examination for static mechanical allodynia, dynamic mechanical allodynia, thermal allodynia, and hyperalgesia. Patients were assigned to one dominant pain phenotype according to an a priori analytic hierarchy: neuropathic, nociplastic, and nociceptive pain. Pain intensity was assessed using the VAS, pain catastrophizing by the Pain Catastrophizing Scale, disability by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and quality of life by the 36-item Short Form Health Survey (SF-36).RESULTS: According to the classification hierarchy, 29 patients (14.5%) had possible neuropathic pain, 22 (11.0%) had neuropathic pain, 35 (17.5%) had possible nociplastic pain, 61 (30.5%) had probable nociplastic pain, and 53 (26.5%) had nociceptive pain. VAS, WOMAC, and Pain Catastrophizing Scale scores differed significantly across pain phenotype groups (all p<0.001). Patients with possible neuropathic, neuropathic, and probable nociplastic pain generally showed greater pain intensity, disability, and pain catastrophizing than those with nociceptive pain. SF-36 physical and mental component scores also differed significantly between groups, with the lowest scores generally observed in the probable nociplastic and possible neuropathic groups.CONCLUSION: Chronic pain after TKA is mechanistically heterogeneous, and approximately three quarters of the present cohort showed possible or likely neuropathic or nociplastic features. These findings support structured mechanism-based evaluation before and after TKA, while also emphasizing the need for prospective studies including preoperative pain phenotyping and standardized sensory testing.

Introduction:Brain β-amyloid (Aβ) accumulation is a hallmark of Alzheimer's disease, but noninvasive detection remains challenging. Blood transcriptomics may provide accessible biomarkers associated with Aβ pathology. Methods:We integrated peripheral blood transcriptomic profiling and MRI-derived structural metrics from 48 individuals across the cognitive continuum, including subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia, stratified by Aβ-PET status. Predictive models were constructed using leave-one-out cross-validation (LOOCV), and selected genes were validated by qRT-PCR. Results:Cross-stage analysis identified RUNX1T1 and COL14A1 as consistently downregulated in Aβ-positive individuals regardless of clinical stage. A predictive model incorporating these two genes demonstrated moderate discrimination of Aβ-PET status in internal leave-one-out cross-validation (LOOCV) evaluation (AUC = 0.81). In addition, COL14A1 expression was associated with cortical thickness and hippocampal volume, whereas RUNX1T1 was primarily associated with hippocampal structure. Among individuals with MCI or dementia, HCN1 and NRG3 were upregulated, whereas KCNMB2 was downregulated in Aβ-positive subjects. A three-gene model based on these markers achieved an LOOCV AUC of 0.79. Discussion:These findings indicate that peripheral blood transcriptomic alterations are associated with Aβ pathology across clinical groups. RUNX1T1 and COL14A1 represent candidate peripheral biomarkers associated with Aβ pathology, while the observed molecular signatures and their associations with brain structural measures provide a basis for further validation in larger, longitudinal cohorts and mechanistic studies.