Current Alzheimer research最新文献

{"title":"Integrative Perspectives on Neurodegeneration and Aging: From Molecular Insights to Therapeutic Strategies.","authors":"Jitendra Kumar Sinha, Shampa Ghosh","doi":"10.2174/0115672050443568250926174642","DOIUrl":"https://doi.org/10.2174/0115672050443568250926174642","url":null,"abstract":"","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research Progress on the Pathogenesis, Therapeutic Strategies, and Phthalocyanine Compounds for Alzheimer's Disease.","authors":"Ruochen Wang, Xiao Yang","doi":"10.2174/0115672050406141250822082635","DOIUrl":"https://doi.org/10.2174/0115672050406141250822082635","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a formidable and complex neurodegenerative disorder driven by multifactorial interactions, including amyloid-beta (Aβ) aggregation, neurofibrillary tangles, and neuroinflammation etc. Current therapies mainly consist of cholinesterase inhibitors and NMDA receptor antagonists, which can alleviate symptoms but fail to reverse disease progression. In recent years, emerging approaches such as immunotherapy and gene therapy have shown potential but remain in clinical exploration. Phthalocyanine (Pc) compounds, with their ability to inhibit Aβ fibril formation, favorable biocompatibility, and optical properties, have demonstrated potential in AD diagnosis and treatment. This review discusses the pathogenesis, therapeutic strategies, and research progress of Pc compounds in AD. Furthermore, the elucidation of their mechanisms of action, the optimization of blood-brain barrier penetration, and the promotion of clinical translation are needed to provide new directions for AD therapy.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Study on the Neuroprotective Effects of Dengzhan Shengmai Capsule on Brain Structure and Cognitive Function in Patients with Vascular Cognitive Impairment.","authors":"Mengyuan Li, Dandan Wang, Dongfeng Wei, Junying Zhang, Xiangwei Dai, Zhanjun Zhang, He Li","doi":"10.2174/0115672050405934250902112132","DOIUrl":"https://doi.org/10.2174/0115672050405934250902112132","url":null,"abstract":"<p><strong>Introduction: </strong>Vascular Cognitive Impairment (VCI) is a common type of dementia that affects the quality of life and lacks effective treatments. The Dengzhan Shengmian capsule (DZSM), a traditional Chinese medicine, is clinically used to alleviate VCI symptoms, but its therapeutic mechanisms are not fully understood. This study aimed to evaluate the neuroprotective effects of DZSM in VCI patients by investigating its impact on cognitive function and brain structure, thereby providing neuroimaging evidence for its clinical application.</p><p><strong>Methods: </strong>A randomized, double-masked, 6-month trial was conducted with 100 VCI patients, assigned to either the experimental group receiving DZSM (n = 50) or the placebo group (n = 50). The efficacy of DZSM in VCI patients was assessed through cognitive behavioral assessments and neuroimaging data collected at baseline and after 6 months. A comparison was made across groups to determine cognitive and neural changes associated with the intervention.</p><p><strong>Results: </strong>Participants receiving DZSM exhibited significant improvements across multiple cognitive domains compared to the placebo, including global cognition (MMSE, p = 0.019; ADASCog, p < 0.001), episodic memory (AVLT-N1N5, p < 0.001), visuospatial ability (CDT, p = 0.034), and working memory (DST, p = 0.015). For brain structure, the gray matter volume in the right postcentral and precentral gyrus, bilateral cuneus, left supplementary motor area, superior occipital gyrus, right hippocampus, right thalamus, bilateral lingual gyrus, left precuneus, right inferior frontal gyrus (triangular part), left inferior parietal gyrus, left superior medial frontal gyrus, right superior temporal gyrus, left middle temporal gyrus, and right parahippocampal gyrus increased in the DZSM group (FDR-corrected, p<0.05), with no significant changes in white matter microstructure. Moreover, gray matter volume increases positively correlated with improvements in global cognition and visuospatial function.</p><p><strong>Discussion: </strong>DZSM capsules significantly improved multiple cognitive domains in VCI patients, particularly memory, visuospatial, and executive functions. The observed increases in gray matter volume suggest that DZSM may exert neuroprotective effects through structural brain remodeling, which is closely associated with cognitive enhancement.</p><p><strong>Conclusion: </strong>This study identifies brain structural abnormalities in VCI patients that correlate with cognitive deficits. DZSM capsule treatment significantly improved cognitive function. While the underlying mechanisms remain to be fully elucidated, these effects may be related to structural changes in the brain.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling Role of Gut Microbiota in Alzheimer's Disease: Mechanisms, Challenges and Future Perspectives.","authors":"R Pavithra, N V Kanimozhi, L Sonali, Chinta Suneetha, M Sukumar","doi":"10.2174/0115672050403066250904112611","DOIUrl":"https://doi.org/10.2174/0115672050403066250904112611","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative condition characterized by neuroinflammation, tau hyperphosphorylation, Aβ (Amyloid beta) accumulation, and synaptic dysfunction. New research indicates that the gut-brain axis, a network of two-way communication that involves immunological signals, neural pathways, and microbial metabolites, makes dysbiosis of the gut microbiota essential to the pathogenesis of AD. Alterations in the gut microbiota's composition hinder the production of crucial metabolites, such as short-chain fatty acids, trimethylamine- N-oxide, and secondary bile acids, which affect neuroinflammatory cascades, mitochondrial bioenergetics, and synaptic plasticity. Furthermore, Toll-like receptor 4 -4-mediated microglial responses are triggered by Gram-negative bacterial lipopolysaccharides. This cascade promotes oxidative stress, chronic neuroinflammation, and disruption of the (BBB) blood-brain barrier, all of which encourage the accumulation of neurotoxic proteins. Microbiome-modulating therapies, such as probiotics, prebiotics, and synbiotics, have been shown to have neuroprotective properties. They work by restoring microbial diversity, increasing (Short-chain fatty acids) SCFA-mediated anti-inflammatory pathways, and reducing glial activation. In addition to promoting gut microbiota equilibrium, dietary approaches like the Mediterranean and ketogenic diets, which are enhanced with polyphenols and omega-3 fatty acids, also lower systemic inflammation and increase neural resilience. Furthermore, the potential of postbiotics and fecal microbiota transplantation to attenuate AD-related neurodegeneration and restore gut-derived metabolic balance is being investigated. Translating these methods into standardized clinical applications is difficult, though, because individual microbiome composition varies. It will be essential to address these complications through mechanistic research and extensive clinical trials to establish gut microbiota as a promising therapeutic target in AD.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145082908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing Alzheimer's Disease Diagnosis Using VGG19 and XGBoost: A Neuroimaging-Based Method.","authors":"Abdelmounim Boudi, Jingfei He, Isselmou Abd El Kader, Xiaotong Liu, Mohamed Mouhafid","doi":"10.2174/0115672050393604250904081342","DOIUrl":"https://doi.org/10.2174/0115672050393604250904081342","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease (AD) is a progressive neurodegenerative disorder that currently affects over 55 million individuals worldwide. Conventional diagnostic approaches often rely on subjective clinical assessments and isolated biomarkers, limiting their accuracy and early-stage effectiveness. With the rising global burden of AD, there is an urgent need for objective, automated tools that enhance diagnostic precision using neuroimaging data.</p><p><strong>Methods: </strong>This study proposes a novel diagnostic framework combining a fine-tuned VGG19 deep convolutional neural network with an eXtreme Gradient Boosting (XGBoost) classifier. The model was trained and validated on the OASIS MRI dataset (Dataset 2), which was manually balanced to ensure equitable class representation across the four AD stages. The VGG19 model was pre-trained on ImageNet and fine-tuned by unfreezing its last ten layers. Data augmentation strategies, including random rotation and zoom, were applied to improve generalization. Extracted features were classified using XGBoost, incorporating class weighting, early stopping, and adaptive learning. Model performance was evaluated using accuracy, precision, recall, F1-score, and ROC-AUC.</p><p><strong>Results: </strong>The proposed VGG19-XGBoost model achieved a test accuracy of 99.6%, with an average precision of 1.00, a recall of 0.99, and an F1-score of 0.99 on the balanced OASIS dataset. ROC curves indicated high separability across AD stages, confirming strong discriminatory power and robustness in classification.</p><p><strong>Discussion: </strong>The integration of deep feature extraction with ensemble learning demonstrated substantial improvement over conventional single-model approaches. The hybrid model effectively mitigated issues of class imbalance and overfitting, offering stable performance across all dementia stages. These findings suggest the method's practical viability for clinical decision support in early AD diagnosis.</p><p><strong>Conclusion: </strong>This study presents a high-performing, automated diagnostic tool for Alzheimer's disease based on neuroimaging. The VGG19-XGBoost hybrid architecture demonstrates exceptional accuracy and robustness, underscoring its potential for real-world applications. Future work will focus on integrating multimodal data and validating the model on larger and more diverse populations to enhance clinical utility and generalizability.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145082893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Cognitive Demand and Imaginability on Semantic Cognition in Patients with Primary Progressive Aphasia.","authors":"Jonatan Ferrer Aragón, Bernarda Téllez-Alanís, Adela Hernández-Galván, Ana Luisa Sosa Ortiz","doi":"10.2174/0115672050395866250904102045","DOIUrl":"https://doi.org/10.2174/0115672050395866250904102045","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Primary progressive aphasia (PPA) is a clinical syndrome characterized by progressive language impairment. Three subtypes have been identified: semantic (svPPA), nonfluent (nfPPA), and logopenic (lvPPA). Although clinical criteria exist to classify these subtypes, the specific ways in which semantic cognition is impaired across these variants have not yet been fully elucidated. This cross-sectional study aimed to analyze the effects of cognitive demand and imaginability on semantic cognition in patients with PPA.</p><p><strong>Methods: </strong>Fifteen patients with PPA (five per variant) and 20 healthy controls completed a semantic association task comprising 20 items. The task included two levels of cognitive demand (low and high) and two types of concepts (concrete and abstract). Participants selected the word with the strongest semantic link to a probe word, based on synonymy, categorical relations, or shared features. Accuracy and reaction times were recorded and analyzed using nonparametric statistics.</p><p><strong>Results: </strong>All PPA groups performed significantly worse than controls, showing fewer correct responses and longer reaction times. svPPA patients exhibited the greatest impairment across all conditions. nfPPA patients performed similarly to controls with concrete concepts but showed deficits with abstract words. lvPPA patients experienced greater difficulty under high cognitive demand, particularly with abstract words, indicating impaired semantic control.</p><p><strong>Discussion: </strong>These findings suggest that svPPA is characterized by global impairment of conceptual knowledge, whereas nfPPA and lvPPA exhibit more selective deficits depending on concept type and cognitive demand.</p><p><strong>Conclusion: </strong>The research herein highlights the importance of considering cognitive demand and imaginability when assessing semantic cognition in PPA.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145082885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arsenic Exposure Induces Cognitive Impairment in Mice with Increased Acetylcholinesterase Activity and Inflammation in the Cortex and Hippocampus: Implications for Alzheimer's Disease.","authors":"Ankumoni Dutta, Banashree Chetia Phukan, Rubina Roy, Pallab Bhattacharya, Diwakar Kumar, Anupom Borah","doi":"10.2174/0115672050390649250904100840","DOIUrl":"https://doi.org/10.2174/0115672050390649250904100840","url":null,"abstract":"<p><strong>Introduction: </strong>Arsenic, a metalloid, is well associated as a risk factor for the development and progression of neurodegenerative diseases, including Alzheimer's Disease (AD), which is characterized by impairment in cognition. However, specific effects of arsenic on Acetylcholinesterase (AChE) activity and inflammatory markers in different brain regions, as well as its impact on behaviour, are not yet fully understood.</p><p><strong>Methods: </strong>Arsenic was administered (20 mg/kg by gavage for 4 weeks) to male and female mice, and its effects on behaviour were assessed by using the object recognition memory test and lightdark box test. AChE activity and neuronal Nitric Oxide (nNOS) were assessed by histoenzymology, and immunohistochemistry was employed for assessment of Glial Fibrillary Acidic Protein (GFAP).</p><p><strong>Results: </strong>Both the behavioural tests showed significant impairment of learning and memory functions and development of psychiatric abnormalities in arsenic-fed mice. The histoenzymology and immunohistochemistry analysis of the cortex and hippocampus region of these arsenic-fed mice revealed the increment of AChE activity and inflammatory markers, viz. GFAP and nNOS.</p><p><strong>Discussion: </strong>The observed increment in AChE activity in the cortex and hippocampus of arsenic-fed mice may contribute to the impairment of learning and memory functions, as well as to the development of psychiatric abnormalities. Furthermore, the enhancement of inflammatory processes in these brain regions may be either a consequence or a contributing factor to the elevated AChE activity, thus establishing a self-fuelling cycle of neuroinflammation and increased AChE activity.</p><p><strong>Conclusion: </strong>Given the gender bias in neurodegenerative diseases, our findings indicate that arsenic exposure does not lead to significant differences in neuropathological and neurobehavioural outcomes between male and female mice. Moreover, current outcomes underscore the potential of arsenic to act as a neurotoxic agent in AD development.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of GSK-3 Inhibition in Alzheimer's Disease Therapy.","authors":"Hala Algazzawi, Jakleen Abujamai, Asim Muhammad Alshanberi, Rukhsana Satar, Shakeel Ahmed Ansari","doi":"10.2174/0115672050400781250904082943","DOIUrl":"https://doi.org/10.2174/0115672050400781250904082943","url":null,"abstract":"<p><p>A serine/threonine kinase with a wide variety of substrates, Glycogen Synthase Kinase-3 (GSK-3) is widely expressed. GSK-3 is a key player in cell metabolism and signaling, modulating numerous cellular functions and playing significant roles in both healthy and diseased states. The two histopathological features of Alzheimer's disease, the intracellular neurofibrillary tangles composed of hyperphosphorylated tau, and the extracellular senile plaques composed of beta-amyloid, have been linked to GSK-3. It alters multiple tau protein locations found in neurofibrillary tangles. Additionally, GSK-3 can react to this peptide and regulate the production of beta-amyloid. The overexpression of GSK-3 in several transgenic models has been linked to tau hyperphosphorylation, neuronal death, and a reduction in cognitive function. It has been shown that lithium, a medication commonly used to treat affective disorders, inhibits GSK-3 at therapeutically relevant concentrations and stops tau phosphorylation. In this review, we provide an overview of the most recent research on the potential of GSK-3 inhibitors for treating Alzheimer's disease.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145017108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Association between the rs6656401 Locus of the CR1 Gene and Structural Alterations of Brain Effects in Han Chinese Patients with Alzheimer's Disease.","authors":"Shu-Yun Zhou, Han-Xiao Lin, Jia-Ming Tang, Qing-Yu Yao, Jia-Wei Hu, Wen-Jun Long, Wen-Zhuo Dai, Tao Ma, Xi-Chen Zhu","doi":"10.2174/0115672050397092250823195514","DOIUrl":"https://doi.org/10.2174/0115672050397092250823195514","url":null,"abstract":"<p><strong>Introduction: </strong>The complement receptor 1 (CR1) gene is identified as the one closely associated with Alzheimer's disease (AD). However, there has been no exploration of the imaging alterations associated with the CR1 gene in AD patients of the Han population. The purpose of this study is to investigate the association between the rs6656401 mutation and neuroimaging variations in Han AD patients.</p><p><strong>Methods: </strong>We collected nuclear magnetic resonance images from 101 patients with AD and 98 healthy controls (HC). The subjects in this study, based on the different genotypes of rs6656401, were divided into three groups, with the number of AA, AG, and GG genotypes in the AD group being 1, 17, and 83, and 1, 8, and 89 in the HC group. Data were analyzed using the dominant model. Structural differences in the brain tissue between genotypes at the rs6656401 polymorphic locus were compared using voxel-based morphological analysis, cortical thickness, and graph-theoretic analysis to construct structural networks.</p><p><strong>Results: </strong>Seven regions (namely, right precuneus, right caudal middle frontal cortical, right rostral middle frontal, right superior frontal, right bankssts, right superior parietal, and right paracentral) were significantly different across CR1 rs6656401 genotypes. The voxel-based morphometry analysis revealed that voxel cluster sizes in the left cerebellum, left superior temporal gyrus, right superior frontal gyrus orbital, right precuneus, and right superior parietal were significantly different in the AA, AG, and GG groups. The degree centrality (Dc) of the left inferior frontal gyrus was significantly greater in the GG group than in the AG group after false discovery rate correction in the structural network analysis.</p><p><strong>Discussion: </strong>This study demonstrates that the rs6656401 AA genotype primarily induces structural alterations in the frontal, temporal, and parietal lobes of AD patients, with significant changes in the right middle frontal gyrus, precuneus, and superior parietal gyrus, along with Dc index alterations in the left inferior frontal gyrus affecting brain network function. Our findings confirm the association between the rs6656401 polymorphism and AD-related brain structural changes, providing the first evidence of these regional alterations in Han Chinese AD cohorts. Future studies will elucidate the locus's pathological mechanism to inform early diagnosis and targeted therapies.</p><p><strong>Conclusion: </strong>Our study first indicated that CR1 rs6656401 genotypes significantly influenced the morphological and structural covariate networks in Han AD patients.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145017086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network Pharmacology of miR-146a-5p as a Potential Anti-Inflammatory Agent in Preventing Alzheimer's Disease.","authors":"Sinjye Lee, Jhibiau Foo, Yokekeong Yong, Qihao Daniel Looi, Yinyin Ooi","doi":"10.2174/0115672050383519250825060815","DOIUrl":"https://doi.org/10.2174/0115672050383519250825060815","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease is expressed as chronic neuroinflammation in the brain, which results in neuronal dysfunction, aberrant protein folding, and declining cognitive abilities. miR-146a-5p is a potent anti-inflammatory agent that can be used to treat several inflammatory diseases, as well as promote wound healing. Our research aimed to utilize network pharmacology to elucidate the therapeutic potential of miR-146a-5p in treating Alzheimer's disease using a biocomputational approach.</p><p><strong>Method: </strong>Alzheimer's disease genes were extracted from DisGeNET, OMIM, and GeneCards databases. At the same time, miR-146a-5p candidate genes were sourced from four prediction databases: miRDB, miRWalk, miRNet, and TargetScan.</p><p><strong>Results: </strong>The overlap between miR-146a-5p and Alzheimer's disease genes was established using STRING, with a score greater than 0.9, revealing a total of 157 nodes in the compound-target disease network.</p><p><strong>Discussions: </strong>Pathway enrichment analysis further revealed key candidate genes associated with Alzheimer's, including those involved in neuronal death, leukocyte migration, and axon development. EGFR, IL6, NFKB1, TLR4, CXCL8, FN1, CXCR4, and BCL2 were pinpointed as the top 8 key candidate genes of miR-146a-5p. Between these key candidate genes, the miR-146a-5p Regulatory Network also demonstrated that miR-146a-5p downregulates EGFR and CXCR4. Furthermore, this research revealed the regulatory network of miR-146a-5p, which modulates the transcriptional activities of IL6, NFKB1, TLR4, CXCL8, FN1, and BCL2.</p><p><strong>Conclusion: </strong>Therefore, the current network pharmacology study explored the principal mechanism behind the anti-inflammatory effects of miR-146a-5p in treating Alzheimer's disease, and potentially to be applied to other neurodegenerative diseases.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145017094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}