Disease Models Research Articles

Suppressing DUSP16 overexpression induced by ELK1 promotes neural progenitor cell differentiation in mouse models of Alzheimer's disease.

Emerged evidence indicated that stimulating hippocampal neurogenesis is a potential strategy for restoring cognition in AD. Mitogen-activated protein kinases (MAPKs) play an essential role in neurogenesis. Meanwhile, the enzymatic power of the phosphatases is much greater than that of kinases. Dual-specificity phosphatase 16 (DUSP16), known to as a phosphatase negatively regulate MAPKs, may be implicated in neural differentiation. Nevertheless, the effect of DUSP16 on cognitive disorders by stimulating neural progenitor cell (NPC) differentiation in AD mice remains unclear. Our study demonstrates an association between DUSP16 SNPs and clinical progression in individuals with mild cognitive impairment (MCI). Besides, increased DUSP16 expression was detected in both 3xTg and SAMP8 mouse models of AD, accompanied by NPC neural differentiation impairments. By silencing DUSP16, the induction of neural differentiation, synaptic transmission, and cognitive benefits were observed in both AD mice. Furthermore, DUSP16 was involved in the process of NPC differentiation through regulating c-Jun N-terminal kinase (JNK) phosphorylation and SOX2 expression. Moreover, ETS transcription factor (ELK1) was involved in the DUSP16 transcription, which resulted in the upregulation of DUSP16 at the state of AD. Our data uncovers a potential regulatory role for DUSP16 in adult hippocampal neurogenesis (AHN) and provides a possibility to find a novel strategy for AD intervention.

Dendrite injury triggers neuroprotection in Drosophila models of neurodegenerative disease.

Dendrite defects and loss are early cellular alterations observed across neurodegenerative diseases that play a role in early disease pathogenesis. Dendrite degeneration can be modeled by expressing pathogenic polyglutamine disease transgenes in Drosophila neurons in vivo. Here, we show that we can protect against dendrite loss in neurons modeling neurodegenerative polyglutamine diseases through injury to a single primary dendrite branch. We find that this neuroprotection is specific to injury-induced activation of dendrite regeneration: neither injury to the axon nor injury just to surrounding tissues induces this response. We show that the mechanism of this regenerative response is stabilization of the actin (but not microtubule) cytoskeleton. We also demonstrate that this regenerative response may extend to other neurodegenerative diseases. Together, we provide evidence that activating dendrite regeneration pathways has the potential to slow-or even reverse-dendrite loss in neurodegenerative disease.

Dopamine loss alters glutamate synapses and transporters in the medial prefrontal cortex and anxiety-related behaviour in a male MPTP rodent model of Parkinson's disease.

Anxiety is a prominent non-motor symptom of Parkinson's disease (PD). Changes in the B-spectrum recordings in PD patients of the prefrontal cortex correlate with increased anxiety. Using a rodent model of PD, we reported alterations in glutamate synapses in the striatum and substantia nigra following dopamine (DA) loss. We hypothesize that DA loss will result in increased anxiety-related behaviours and that this will be associated with alterations in glutamate synapses and transporters within the medial prefrontal cortex (mPFC). Following 4weeks of progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration, there was an increase in anxiety-related behaviours and a 78% decrease in plasma corticosterone levels versus the vehicle (VEH)-treated mice. This was associated with a 30% decrease in the density of dendritic spines in Layers Il/Ill, and a 53% decrease in the density of glutamate immuno-gold labelling within vesicular glutamate transporter 1 (Vglut1)-labelled nerve terminals and spines, with no change within vesicular glutamate transporter 2 (Vglut2) positive terminals/spines in the MPTP versus VEH groups. Our prior work determined that a decrease in striatal glutamate terminal density was associated with an increase in extracellular glutamate levels. There was an increase in protein expression of Vglut1 (40%), Vglut2 (37%) and glutamate aspartate transporter (GLAST) (225%), and a decrease in glutamate transporter 1 (GLT-1) (50%) and excitatory amino acid carrier 1 (EAAC1) (51%), in the MPTP versus VEH groups within the mPFC. These data suggest that the decrease in dendritic spines within the mPFC following nigrostriatal DA loss may be due to increased extracellular glutamate levels (decrease in glutamate transporters), leading to an increase in anxiety-related behaviours.

Near-infrared light stimulation regulates neural oscillation and memory behavior of mice with Alzheimer’s disease

Photobiomodulation (PBM) is a non-invasive neuromodulation technique for the brain. Low-intensity near-infrared light (1–500 mw) has demonstrated the ability to improve memory in Alzheimer’s disease (AD) model mice, suggesting its potential for AD treatment. However, the impact of PBM on neural oscillations in the hippocampal region affected by AD remains unknown. In this study, AD model mice were subjected to PBM for 60 days and then tested using novel object recognition behavior (NOR) experiments. During behavioral experiments, local field potential signals (LFP) of the mice was recorded using a single electrode in the CA1 region to analyze memory ability and neural oscillation characteristics. The results revealed that mice stimulated with PBM exhibited significantly higher new object differentiation indices compared to the Sham group (p < 0.01). Furthermore, PBM stimulation led to a significant increase in relative power and sample entropy of theta and gamma bands (p < 0.01). The coupling intensities of θ-low-γ and θ-high-γ were also significantly higher in the PBM group compared to the Sham group (p < 0.01). In conclusion, these findings suggest that PBM may improve memory ability in AD mice through regulation of neural oscillation characteristics, providing a theoretical basis for utilizing PBM as a treatment modality for Alzheimer’s disease.

Goji Disease and Pest Monitoring Model Based on Unmanned Aerial Vehicle Hyperspectral Images

Combining near-earth remote sensing spectral imaging technology with unmanned aerial vehicle (UAV) remote sensing sensing technology, we measured the Ningqi No. 10 goji variety under conditions of health, infestation by psyllids, and infestation by gall mites in Shizuishan City, Ningxia Hui Autonomous Region. The results indicate that the red and near-infrared spectral bands are particularly sensitive for detecting pest and disease conditions in goji. Using UAV-measured data, a remote sensing monitoring model for goji pest and disease was developed and validated using near-earth remote sensing hyperspectral data. A fully connected neural network achieved an accuracy of over 96.82% in classifying gall mite infestations, thereby enhancing the precision of pest and disease monitoring in goji. This demonstrates the reliability of UAV remote sensing. The pest and disease remote sensing monitoring model was used to visually present predictive results on hyperspectral images of goji, achieving data visualization.

Acute transcutaneous auricular vagus nerve stimulation modulates presynaptic SV2A density in healthy rat brain: An invivo microPET study.

Vagus nerve stimulation (VNS) is the subject of exploration as an adjunct treatment for neurological disorders such as epilepsy, chronic migraine, pain, and depression. A non-invasive form of VNS is transcutaneous auricular VNS (taVNS). Combining animal models and positron emission tomography (PET) may lead to a better understanding of the elusive mechanisms of taVNS. We evaluated the acute effect of electrical stimulation of the left vagus nerve via the ear on brain synaptic vesicle glycoprotein 2A (SV2A) as a measure of presynaptic density and glucose metabolism in naïve rats. Female Sprague-Dawley rats were imaged with [11C]UCB-J (n = 11) or [18F]fluorodeoxyglucose ([18F]FDG) PET (n = 13) on two separate days, (1) at baseline, and (2) after acute unilateral left taVNS or sham stimulation (30 min). We calculated the regional volume of distribution (VT) for [11C]UCB-J and standard uptake values (SUV) for [18F]FDG. We observed regional reductions of [11C]UCB-J binding in response to taVNS ranging from 36% to 59%. The changes in taVNS compared to baseline were significantly larger than those induced by sham stimulation. The differences were observed bilaterally in the frontal cortex, striatum, and midbrain. The [18F]FDG PET uptake remained unchanged following acute taVNS or sham stimulation compared to baseline values. This proof-of-concept study shows for the first time that acute taVNS for 30 min can modulate invivo synaptic SV2A density in cortical and subcortical regions of healthy rats. Preclinical disease models and PET ligands of different targets can be a powerful combination to assess the therapeutic potential of taVNS.

Myeloid gasdermin D drives early-stage T cell immunity and peripheral inflammation in a mouse model of Alzheimer's disease.

It is now realized that peripheral inflammation and abnormal immune responses, especially T cells, contribute to the development of Alzheimer's disease (AD). Gasdermin D (GSDMD) -mediated pyroptosis has been associated with several neuroinflammatory diseases, but whether GSDMD is involved in the peripheral inflammation and T cell immunity during AD remains unclear. We dynamically investigated GSDMD activation in the peripheral and central nervous system of 5×FAD mouse model and dissected the role of myeloid GSDMD using genetic knockout mice, especially its influence on peripheral T cell responses and AD inflammation. RNA sequencing and in vitro coculture were used to elucidate the underlying immune mechanisms involved. Targeted inhibitor experiments and clinical correlation analysis were used to further verify the function of GSDMD in AD. In the present study, caspase activated GSDMD in the spleen of 5×FAD mice earlier than in the brain during disease progression. Loss of myeloid cell GSDMD was shown to impair early-stage effector T cell activation in the periphery and prevent T cell infiltration into the brain, with an overall reduction in neuroinflammation. Furthermore, myeloid cell GSDMD induced T cell PD-1 expression through the IL-1β/NF-κB pathway, restricting regulatory T cells. The administration of a GSDMD inhibitor combined with an anti-PD-1 antibody was found to mitigate the development of AD-associated inflammation. In some AD patients, plasma sPD-1 is positively correlated with IL-Iβ and clinical features. Our study systematically identified a role for GSDMD in the AD-related peripheral inflammation and early-stage T cell immunity. These findings also suggest the therapeutic potential of targeting GSDMD for the early intervention in AD.

Amyloid pathology and cognitive impairment in hAβ-KI and APPSAA-KI mouse models of Alzheimer's disease

The hAβ-KI and APPSAA-KI are two amyloid models that harbor mutations in the endogenous mouse App gene. Both hAβ-KI and APPSAA-KI mice contain a humanized Aβ sequence, and APPSAA-KI mice carry three additional familial AD mutations. We herein report that the Aβ levels and Aβ42/Aβ40 ratio in APPSAA-KI homozygotes are dramatically higher than those in hAβ-KI homozygotes at 14 months of age. In addition, APPSAA-KI mice display a widespread distribution of amyloid plaques in the brain, whereas the plaques are undetectable in hAβ-KI mice. Moreover, there are no sex differences in amyloid pathology in APPSAA-KI mice. Both APPSAA-KI and hAβ-KI mice exhibit cognitive impairments, wherein no significant differences are found between these two models, although APPSAA KI mice show a trend towards worse cognitive function. Notably, female hAβ-KI and APPSAA-KI mice have a more pronounced cognitive impairments compared to their respective males. Our findings suggest that Aβ humanization contributes to cognitive deficits in APPSAA-KI mice, and that amyloid deposition might not be closely associated with cognitive impairments in APPSAA-KI mice.

Comparison of Different Prognostic Scoring Systems in Predicting the Severity and Outcome in Alcoholic Hepatitis in Indian Patients

Abstract Introduction: Alcohol abuse causes a variety of liver diseases including alcoholic steatosis, alcoholic hepatitis (AH), liver fibrosis, cirrhosis, and hepatocellular carcinoma. AH is a clinical syndrome which typically occurs after the harmful use of alcohol. There are mild forms that are likely to improve with conservative management, whereas severe cases are associated with a high mortality rate and have a high risk of death despite treatment. The identification of severe AH is important, as this can be associated with 30%–50% short-term mortality. Existing prognostic scores have been validated in the western population, and the data of application in the Indian population are scant. Materials and Methods: It is a prospective observational study conducted for 2 years at Tertiary Care Hospital Army Hospital (Research and Referral) Delhi. The sample size was kept to be 45. For each patient, clinical and laboratory values were obtained on the day of admission and used to calculate the prognostic models according to their formulas. The various scores – Maddrey’s discriminant function (mDF), Glasgow AH score (GAHS), age, bilirubin, international normalized ratio (INR), creatinine score, and model of end-stage liver disease (MELD) including its modification MELD-sodium were calculated. For patients started on steroids, early changes in bilirubin level and Lille score were calculated. Results: All the prognostic scores were found to be good predictors of mortality. When compared with each other, MELD was most indicative of mortality with maximum area under the receiver operating characteristic curve. All the scores were significantly higher in the nonsurvivors than the survivors (P < 0.0001). Conclusion: AH is a clinical syndrome that occurs after the harmful use of alcohol and confers a high mortality. Effective treatment and support for patients with AH is dependent on a proper assessment of the disease severity and estimation of the risk of death as early in the course of the disease as possible.

Establishment of an induced pluripotent stem cell line (SDCHi011-A) from a healthy Chinese female donor

We generated an induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells (PBMCs) of a healthy 40-year-old Chinese Han female, using non-integrated reprogramming technology. The established iPSC line, SDCHi011-A, expressed pluripotency marker and could differentiate into cells of three germ layers in vitro with normal karyotype. This cell line is a valuable resource as a control line for stem cell research of disease models and molecular pathogenesis.

Corticostriatal Maldevelopment in the R6/2 Mouse Model of Juvenile Huntington's Disease.

There is a growing consensus that brain development in Huntington's disease (HD) is abnormal, leading to the idea that HD is not only a neurodegenerative but also a neurodevelopmental disorder. Indeed, structural and functional abnormalities have been observed during brain development in both humans and animal models of HD. However, a concurrent study of cortical and striatal development in a genetic model of HD is still lacking. Here we report significant alterations of corticostriatal development in the R6/2 mouse model of juvenile HD. We examined wildtype (WT) and R6/2 mice at postnatal (P) days 7, 14, and 21. Morphological examination demonstrated early structural and cellular alterations reminiscent of malformations of cortical development, and ex vivo electrophysiological recordings of cortical pyramidal neurons (CPNs) demonstrated significant age- and genotype-dependent changes of intrinsic membrane and synaptic properties. In general, R6/2 CPNs had reduced cell membrane capacitance and increased input resistance (P7 and P14), along with reduced frequency of spontaneous excitatory and inhibitory synaptic events during early development (P7), suggesting delayed cortical maturation. This was confirmed by increased occurrence of GABA A receptor-mediated giant depolarizing potentials at P7. At P14, the rheobase of CPNs was significantly reduced, along with increased excitability. Altered membrane and synaptic properties of R6/2 CPNs recovered progressively, and by P21 they were similar to WT CPNs. In striatal medium-sized spiny neurons (MSNs), a different picture emerged. Intrinsic membrane properties were relatively normal throughout development, except for a transient increase in membrane capacitance at P14. The first alterations in MSNs synaptic activity were observed at P14 and consisted of significant deficits in GABAergic inputs, however, these also were normalized by P21. In contrast, excitatory inputs began to decrease at this age. We conclude that the developing HD brain is capable of compensating for early developmental abnormalities and that cortical alterations precede and are a main contributor of striatal changes. Addressing cortical maldevelopment could help prevent or delay disease manifestations.

Growth Factor Gene Therapy for Alzheimer's Disease.

Nervous system growth factors are natural proteins of the brain that influence neuronal survival and function throughout life, from embryonic development to old age. In animal models of Alzheimer's disease (AD), the growth factor brain derived neurotrophic factor (BDNF) prevents neuronal death, activates neuronal function, builds new synapses and improves learning and memory. Accordingly, we are determining whether gene delivery of BDNF in patients with AD will slow disease progression and improve memory. In a previous clinical trial of nerve growth factor (NGF) gene therapy in AD patients (NCT00017940, June 2001), we learned that growth factors can unequivocally elicit classic trophic responses from degenerating neurons in AD. Experience gained from the earlier NGF gene therapy trial is guiding our effort to optimize gene delivery of BDNF in our present clinical program (NCT05040217, June 2021).

Incretin Mimetics as Potential Disease Modifying Treatment for Alzheimer's Disease.

Alzheimer's disease is a devastating neurodegenerative condition that exerts a significant global burden. Despite recent efforts, disease modifying therapies remain extremely limited, with a tremendous proportion of patients having to rely on symptomatic treatment only. Epidemiological and pathological overlaps exist between Alzheimer's disease and diabetes mellitus type 2, with people with diabetes mellitus type 2 at a significantly increased risk of developing Alzheimer's disease in the future. Incretin mimetics, also known as GLP-1/GIP receptor agonists, are useful tools licensed for the treatment of diabetes mellitus type 2 which have recently been the subject of news coverage for their off-label use as weight loss medications. Emerging evidence highlights the possible neuroprotective function of incretin mimetics in models of Alzheimer's disease as well as in clinical studies. This review details the pre-clinical and clinical studies that have explored the effectiveness of incretin mimetics to alleviate Alzheimer's disease associated pathology and cognitive impairment, while also highlighting the progress made to examine the effectiveness of these molecules in Parkinson's disease. Should clinical trials prove effective, incretin mimetics may be able to be repurposed and become useful novel tools as disease-modifying treatments for Alzheimer's disease and other neurodegenerative diseases.

Lifespan of male and female APP/PS1 and APP NL-F/NL-F mouse models of Alzheimer's disease.

Alzheimer's disease (AD) disproportionately affects women, yet most preclinical research studies are male-centric. We performed lifespan analyses of male and female AD mouse models (APP/PS1 and APP NL-F/NL-F ) and their shared genetic background control (C57BL/6). Survival curves support significant sex differences between within genotypes. Minimal longevity revealed increased age in male APP/PS1, and decreased age in APP NL-F/NL-F mice. Maximal longevity revealed an increased average age in males. Furthermore, median lifespan differed between sex and genotype. This study supports sexual dimorphic survival in two mouse models of AD, emphasizing the need to examine mechanisms and treatments in both sexes.

Divergent and Convergent TMEM106B Pathology in Murine Models of Neurodegeneration and Human Disease.

TMEM106B is a lysosomal/late endosome protein that is a potent genetic modifier of multiple neurodegenerative diseases as well as general aging. Recently, TMEM106B was shown to form insoluble aggregates in postmortem human brain tissue, drawing attention to TMEM106B pathology and the potential role of TMEM106B aggregation in disease. In the context of neurodegenerative diseases, TMEM106B has been studied in vivo using animal models of neurodegeneration, but these studies rely on overexpression or knockdown approaches. To date, endogenous TMEM106B pathology and its relationship to known canonical pathology in animal models has not been reported. Here, we analyze histological patterns of TMEM106B in murine models of C9ORF72 -related amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD), SOD1-related ALS, and tauopathy and compare these to postmortem human tissue from patients with C9-ALS/FTD, Alzheimer's disease (AD), and AD with limbic-predominant age-related TDP-43 encephalopathy (AD/LATE). We show that there are significant differences between TMEM106B pathology in mouse models and human patient tissue. Importantly, we also identified convergent evidence from both murine models and human patients that links TMEM106B pathology to TDP-43 nuclear clearance specifically in C9-ALS. Similarly, we find a relationship at the cellular level between TMEM106B pathology and phosphorylated Tau burden in Alzheimer's disease. By characterizing endogenous TMEM106B pathology in both mice and human postmortem tissue, our work reveals considerations that must be taken into account when analyzing data from in vivo mouse studies and elucidates new insights supporting the involvement of TMEM106B in the pathogenesis and progression of multiple neurodegenerative diseases.

Aging-dependent loss of functional connectivity in a mouse model of Alzheimer's disease and reversal by mGluR5 modulator.

Amyloid accumulation in Alzheimer's disease (AD) is associated with synaptic damage and altered connectivity in brain networks. While measures of amyloid accumulation and biochemical changes in mouse models have utility for translational studies of certain therapeutics, preclinical analysis of altered brain connectivity using clinically relevant fMRI measures has not been well developed for agents intended to improve neural networks. Here, we conduct a longitudinal study in a double knock-in mouse model for AD (AppNL-G-F/hMapt), monitoring brain connectivity by means of resting-state fMRI. While the 4-month-old AD mice are indistinguishable from wild-type controls (WT), decreased connectivity in the default-mode network is significant for the AD mice relative to WT mice by 6 months of age and is pronounced by 9 months of age. In a second cohort of 20-month-old mice with persistent functional connectivity deficits for AD relative to WT, we assess the impact of two-months of oral treatment with a silent allosteric modulator of mGluR5 (BMS-984923/ALX001) known to rescue synaptic density. Functional connectivity deficits in the aged AD mice are reversed by the mGluR5-directed treatment. The longitudinal application of fMRI has enabled us to define the preclinical time trajectory of AD-related changes in functional connectivity, and to demonstrate a translatable metric for monitoring disease emergence, progression, and response to synapse-rescuing treatment.

Comparison of sGC activator and sGC stimulator in 5/6 nephrectomized rats on high-salt-diet

IntroductionSoluble guanylate cyclase (sGC) stimulators and activators are known to enhance kidney function in various models of chronic kidney disease (CKD) by increasing cyclic guanosine monophosphate (cGMP). Their differential effects on CKD progression, particularly under conditions of oxidative stress, remain unexplored by direct comparative studies.MethodsWe conducted a side-by-side comparison using 5/6 nephrectomized rats on a high salt diet (5/6Nx+HSD) to evaluate the efficacy of the sGC stimulator BAY 41–8543 and the sGC activator BAY 60–2770 in CKD progression. BAY 41–8543 (1 mg/kg; twice daily) and BAY 60–2770 (1 mg/kg; once daily) were administered by gavage for 11 weeks.ResultsThe 5/6Nx+HSD model led to increased plasma creatinine, proteinuria, and blood pressure. Both BAY 41–8543 and BAY 60–2770 significantly reduced systolic and diastolic blood pressure to a similar extent but did not improve renal function parameters. Notably, BAY 60–2770 reduced renal fibrosis, including interstitial fibrosis and glomerulosclerosis, whereas BAY 41–8543 did not. These antifibrotic effects of BAY 60–2770 were independent of blood pressure reduction. Proteomic analysis revealed that BAY 60–2770 corrected the upregulation of 9 proteins associated with apoptosis and fibrosis, including Caspase-3, MKK6 (Mitogen-Activated Protein Kinase Kinase 6), Prdx5 (Peroxiredoxin-5), in the 5/6Nx+HSD group.DiscussionIn contrast, BAY 41–8543 had no significant impact on these proteins. sGC activators were more effective than sGC stimulators in reducing renal fibrosis in 5/6 nephrectomized rats on a high salt diet, and this effect was due to modulation of apoptosis-associated proteins beyond the control of blood pressure.

Revisiting the Prognostic Influences of Donor-Recipient Size Mismatch in Deceased Donor Liver Transplantation.

Liver transplantation (LT) outcomes are influenced by donor-recipient size mismatch. This study re-evaluated the impact on graft size discrepancies on survival outcomes. Data from 53 389 adult LT recipients from the United Network for Organ Sharing database (2013-2022) were reviewed. The study population was divided by the body surface area index (BSAi), defined as the ratio of donor body surface area (BSA) to recipient BSA, into small-for-size (BSAi < 0.78), normal-for-size (BSAi 0.78-1.24), and large-for-size (BSAi > 1.24) grafts in deceased donor LT (SFSD, NFSD, and LFSD). Multivariate Cox regression and Kaplan-Meier survival analyses were conducted. The frequency of size mismatch in deceased donor LT increased over the past 10 y. SFSD had significantly worse 90-d graft survival (P < 0.01), and LFSD had inferior 1-y graft survival among 90-d survivors (P = 0.01). SFSD was hazardous within 90 d post-LT because of vascular complications. Beyond 1 y, graft size did not affect graft survival. LFSD risk within the first year was mitigated with lower model for end-stage liver disease (MELD) 3.0 scores (<35) or shorter cold ischemia time (<8 h). The negative impacts on donor-recipient size mismatch on survival outcomes are confined to the first year post-LT. SFSD is associated with a slight decrease in 90-d survival rates. LFSD should be utilized more frequently by minimizing cold ischemia time to <8 h, particularly in patients with MELD 3.0 scores below 35. These findings could improve donor-recipient matching and enhance LT outcomes.

Evaluating the effects of basil (Ocimum basilicum) in the experimental model of Alzheimer's disease in rats

Evaluating the effects of basil (Ocimum basilicum) in the experimental model of Alzheimer's disease in rats

Coronary heart disease evaluation using PCAT radiomics model based on coronary CT angiography and pericoronary adipose tissue.

To explore the clinical application value of radiomics model based on pericoronary adipose tissue (PCAT) in predicting coronary heart disease. A retrospective analysis was performed for inpatients who had undergone coronary computed tomography angiography from January to December 2023, and 164 cases of coronary artery lesions were screened as the lesion group and 190 cases of normal coronary artery samples were selected as the control group. The clinical data and imaging data of all patients were collected, the radiomics features were extracted by relevant software, and the "region of interest" of pericoronary fat was delineated, and the selection operator and multivariate logistic regression were used to screen the radiomic features of pericoronary fat. A coronary heart disease evaluation model was constructed by the best radiomics features. Area under the curve values of the PCAT radiomics scoring model for predicting the receiver operating characteristic curve of coronary heart disease were 0.863 and 0.851 in training and test sets, respectively. After calibration curve analysis, PCAT radiomics scoring model has a high consistency between the predictive evaluation results and the actual results of coronary heart disease events. In addition, in the training set, the PCAT radiomics scoring model has a net benefit on all threshold probabilities. In the test set, the model has a negative net return with only a small number of threshold probabilities. After combining the clinical characteristics model, the evaluation accuracy of the model for coronary heart disease can reach 0.896. PCAT radiomics model based on coronary computed tomography angiography can effectively predict and evaluate coronary heart disease, which is of great value for the clinical diagnosis of coronary artery disease.