Current Alzheimer research最新文献

{"title":"Metabolic Regulation as a Potential Therapeutic Approach for Alzheimer's Disease.","authors":"Jinmiao Zhong, Jiaxin Sun, Bing Zhou","doi":"10.2174/0115672050379410250421065857","DOIUrl":"https://doi.org/10.2174/0115672050379410250421065857","url":null,"abstract":"<p><p>Lecanemab, a therapeutic antibody designed to target amyloid-beta (Aβ) clearance, has recently been approved by the FDA and introduced in multiple countries, representing a significant milestone in advancing Alzheimer's disease (AD) treatment. However, its limited clinical efficacy underscores the need for further investigation of disease pathogenesis. Emerging evidence suggests that glucose and lipid metabolism dysfunction plays a critical role in AD, with metabolic changes emerging as one of the most significantly altered pathways in the early stage of pathology. These findings highlight the therapeutic potential of targeting metabolic regulation as a strategy to address AD.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060235","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":"Unraveling the Intricacies: The Role of miRNAs in the Progression and Initiation of Alzheimer's Disease","authors":"Forouzan Amerizadeh, Elnaz Farzadifar","doi":"10.2174/0115672050374376250416044512","DOIUrl":"10.2174/0115672050374376250416044512","url":null,"abstract":"<p><strong>Aim: </strong>This study aims to investigate the molecular mechanisms underlying Alzheimer's disease (AD) by analyzing differentially expressed miRNAs and their target proteins to identify key regulatory networks and therapeutic targets.</p><p><strong>Background: </strong>Alzheimer's disease (AD) is a complex neurodegenerative disorder with multifaceted regulatory mechanisms involving differentially expressed miRNAs. Recent studies suggest that understanding the target proteins of these miRNAs may reveal crucial insights into AD pathology.</p><p><strong>Objective: </strong>The objective of this study was to investigate the role of differentially expressed miRNAs in Alzheimer's disease (AD) by identifying their target proteins and exploring the associated regulatory networks. This includes uncovering key hub proteins and their involvement in critical biological pathways linked to AD progression. Additionally, the study aims to identify transcription factors regulating these proteins and evaluate potential therapeutic compounds targeting these molecular players. By integrating these findings, the research seeks to provide a deeper understanding of AD pathogenesis and pave the way for novel therapeutic strategies to mitigate its progression.</p><p><strong>Methods and materials: </strong>Differentially expressed miRNAs were collected from reviews, with target proteins identified using MiRDB, STRING, and Cytoscape. Promoter and transcription factor (TF) analyses were performed using Enrichr, and potential therapeutic compounds targeting hub proteins were explored via DrugBank.</p><p><strong>Results: </strong>This study identifies key hub proteins, including TNF, PTEN, KRAS, ESR1, H3-3B, COL25A1, COL19A1, COL13A1, COL27A1, COL5A3, CCND1, FGF2, SMAD2, and PXDN, exploring their roles in AD progression. GO and KEGG pathway analyses revealed that hub proteins, including TNF, PTEN, KRAS, and ESR1, are involved in essential biological processes related to neural differentiation and signaling. Cytocluster analysis identified clusters with significant associations with AD, indicating complex interaction networks among these proteins.</p><p><strong>Discussion: </strong>Potential therapeutic agents, including TNF inhibitors, estrogen receptor agonists, and KRAS inhibitors, were identified. Promoter and TF analysis further highlighted regulatory factors in AD pathways.</p><p><strong>Conclusion: </strong>This study emphasizes crucial AD-related proteins and pathways, providing insights for future therapeutic targeting of gene expression to mitigate AD progression.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056897","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":"Altered Default Mode Network Connectivity in Mild Cognitive Impairment: Insights from Resting-State fMRI Studies.","authors":"Danqi Zhang, Jinhuan Yue, Hanbin Niu, Zeyi Wei, Dong-Hong Huang, Peng Wang, Xiaoling Li, Yuhui Zhao, Qinhong Zhang","doi":"10.2174/0115672050352061250328055829","DOIUrl":"https://doi.org/10.2174/0115672050352061250328055829","url":null,"abstract":"<p><p>Mild Cognitive Impairment (MCI) is marked by a measurable decline in cognitive function that exceeds typical age-related changes but does not yet qualify as dementia. The brain's Default Mode Network (DMN) remains active during rest and plays a crucial role in introspective processes, such as memory retrieval and self-referential thinking. Resting-state functional magnetic resonance imaging (rs-fMRI) is a non-invasive neuroimaging technique that measures spontaneous fluctuations in blood oxygenation, providing insights into functional connectivity within brain networks. Investigating the DMN using rs-fMRI in individuals with MCI allows researchers to identify early neural changes associated with cognitive decline, which may serve as biomarkers for the early detection of Alzheimer's disease or related dementias. The rs-fMRI technique has been widely used in MCI research to explore the underlying neurobiological mechanisms of cognitive impairment. This study aims to synthesize findings from rs-fMRI studies focusing on alterations in DMN connectivity in MCI populations. This analysis deepens our understanding of the early-stage neural disruptions in MCI and holds significant implications for developing early diagnostic tools and interventions aimed at delaying the progression to dementia.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056755","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":"Influence of Inflammation, Gut Microbiota, and Stress on Cognition and Oral Health Therapies.","authors":"An Liye, Zhou Saichao, Xinliang Zhang, Marina Loktionova, Leonid K Gavrikov, Oleg Glazachev","doi":"10.2174/0115672050361661250327061024","DOIUrl":"https://doi.org/10.2174/0115672050361661250327061024","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Prolonged or repeated psychological stress triggers dental and orthodontic diseases via inflammatory pathways and oxidative stress. This review aims to elucidate the role of inflammation, gut microbiota, stress, and cognition, exploring their impact on the development of therapeutics to enhance oral health.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;The primary aim pertinent to this systematic review is to elucidate the significant implications of cognition and stress in dental and orthodontic health. Specifically, the review aims to (1) investigate the association between emotional stress and the incidence or progression of periodontal disease; (2) explore the impact of physiological and emotional stress on cellular and molecular inflammatory responses in orthodontics; (3) examine the influence of gut-mediated psychophysiological factors on emotional changes in mental health and cognition with a focus on periodontics and orthodontics; and (4) investigate the potential of gut microbiota alterations to influence oral and cognitive/mental health, including the impact of probiotic supplementation and dietary interventions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A systematic review was conducted without comprehensive meta-analysis, focusing on literature from 1960 to 2024. Databases searched included PubMed, Embase, ReleMed, National Library of Medicine (NLM), Scopus, and Google Scholar. Keywords used were \"cognition,\" \"emotional stress,\" \"gut microbiota,\" \"orthodontics,\" \"prosthetics,\" \"pathophysiology,\" and \"mental health.\" Studies were selected based on relevance, publication date, access to full texts, and adherence to PRISMA guidelines. The review integrated findings on the impact of emotional stress on periodontal disease and orthodontic health through pathophysiological implications.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Age-related neurodegeneration causes Alzheimer's disease and severe dementia that subsequently promotes poor oral health. The review identified a complex interplay between emotional stress and periodontal disease. While a direct association remains to be conclusively proven, several studies highlight the influence of stress on the severity and incidence of periodontal disease through inflammatory and immunological pathways. Stress manifests in various ways, such as increased masticatory muscle tone, changes in eating behavior, and the initiation of bruxism, all of which can affect dental health. Physiological stress induces an inflammatory response to orthodontic tooth movement, impacting orthodontic treatment outcomes. Furthermore, the review elucidates the role of gut-mediated psychophysiological factors in emotional changes, influencing periodontal and orthodontic health. Emerging evidence suggests that gut microbiota alterations can significantly impact oral and cognitive health through systemic inflammation and neuroimmune mechanisms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This review highlights the significant impa","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144016349","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":"Relationship between Alzheimer's Disease and Type 2 Diabetes: Critical Review On Cellular and Molecular Common Pathogenic Mechanisms.","authors":"Arantxa Rodríguez-Casado, Mª Isabel Álvarez, José-Joaquín Merino, Adolfo Toledano-Díaz, Adolfo Toledano","doi":"10.2174/0115672050375461250325074826","DOIUrl":"https://doi.org/10.2174/0115672050375461250325074826","url":null,"abstract":"<p><strong>Objective/background: </strong>Type 2 Diabetes Mellitus (T2D) and Alzheimer's disease (AD) are two diseases with a high prevalence today that share common pathophysiological mechanisms, suggesting a potential causal relationship between them. AD is also known as Type 3 Diabetes Mellitus (T3D). A complete understanding of this complex issue (T2D-AD) is necessary to develop fully effective and easily applicable therapies that do not yet exist. A critical update on the subject is presented, delving into the pathophysiological implications and defining new research for promoting new therapeutic interventions.</p><p><strong>Methods: </strong>Revision and critical analysis of the described and observed cellular and molecular common pathogenic T2D-AD mechanisms in human and model studies.</p><p><strong>Results: </strong>Both diseases exhibit common genetic, epigenetic, biochemical and physiological characteristics. Pathogenic mechanisms such as peripheral inflammation, mitochondrial dysfunction, oxidative stress, insulin resistance, hyperglycemia, formation of advanced glycation end products, neuroinflammation, neuroglial dysfunctions, and deposition of aberrant misfolded proteins are commonly displayed in dysmetabolic diseases and AD. The T2D, AD and T2D-AD pathogenic courses present several close key contacts (or identities). The clinical course of T2D has different incidences in the neurodegenerative course of AD (from its onset to its aggravation). There are theoretical, practical and interpretative problems in studies on human and experimental models, as well as in the clinical and pathological interpretation of T2D-AD dementia, which are of great importance in the development of knowledge of this subject and the therapeutic application of its results.</p><p><strong>Conclusion: </strong>In recent years, there has been a great advance in the study of the relationships between T2D (and related dysmetabolic diseases) and AD. There is no doubt about their close relationship and/or the inclusion of AD as a metabolic disease (T3D). Joint therapies seem to be absolutely necessary. Key pathogenic processes (insulin resistance, genetic and epigenetic regulation, peripheral inflammation and neuroinflammation) must be investigated to develop new and effective therapies.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002857","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":"Analysis of the Relationship Between NLRP3 and Alzheimer's Disease in Oligodendrocytes based on Bioinformatics and In Vitro Experiments.","authors":"Chen Li, Yan Chen, Yinhui Yao, Yuxin Zhang, Shu Tong, Yazhen Shang","doi":"10.2174/0115672050376534250310061951","DOIUrl":"https://doi.org/10.2174/0115672050376534250310061951","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Aim: &lt;/strong&gt;This study aims to explore the potential association between nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in oligodendrocytes and Alzheimer's disease (AD), utilizing a combination of bioinformatics analysis and molecular biology experiments to validate this relationship.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Public datasets related to AD were systematically retrieved and downloaded from the Gene Expression Omnibus (GEO) database at the National Center for Biotechnology Information (NCBI). Subsequently, the SVA package was employed to merge the data and eliminate batch effects, allowing for the precise identification of differentially expressed genes (DEGs) between AD patients and healthy controls. Advanced machine learning techniques, including LASSO regression analysis, random forest algorithms, and support vector machines (SVM), were utilized to analyze further the DEGs associated with the NLRP3 inflammasome to determine the gene set most closely related to AD. The effectiveness and clinical value of the gene-based diagnostic model were comprehensively assessed through receiver operating characteristic (ROC) curve analysis, nomogram construction, and decision curve analysis (DCA). Immune infiltration analysis evaluated the extent of various immune cell infiltrations in the brain tissue of AD patients. Single-cell transcriptomics and in vitro experiments were conducted to verify the molecular expression of NLRP3 in oligodendrocytes within the AD model.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 11 significant DEGs were identified, with 4 genes showing downregulation and 7 genes exhibiting upregulation. All three algorithms-LASSO regression, random forest, and SVM-consistently identified PANX1, APP, P2RX7, MEFV, and NLRP3 as key genes closely associated with AD. ROC curve analysis, nomogram modeling, and DCA results demonstrated that the diagnostic model constructed based on these five genes exhibited high diagnostic accuracy and clinical applicability. Immune infiltration analysis revealed a significant correlation between key genes associated with AD and various immune cells, particularly CD8+ T cells, monocytes, activated NK cells, and neutrophils, suggesting that these cells may play important roles in the immunopathological process of AD. Single-cell transcriptomics indicated that the expression level of NLRP3 in oligodendrocytes was higher in the AD group compared to the control group (p &lt; 0.05). Additionally, in vitro cell experiments using RT-PCR, immunofluorescence, and Western blot analysis confirmed that the expression level of NLRP3 in oligodendrocytes was elevated in the AD model relative to the control group (p &lt; 0.05).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study corroborates the high expression of NLRP3 in AD and its close relationship with the disease through integrated bioinformatics analysis and molecular biology experiments. Furthermore, the diagnostic model constructed based on","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047572","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":"Microglial Modulation in Alzheimer's Disease: Central Players in Neuroinflammation and Pathogenesis.","authors":"Md Sadique Hussain, Yumna Khan, Rabab Fatima, Mudasir Maqbool, Prasanna Srinivasan Ramalingam, Mohammad Gayoor Khan, Ajay Singh Bisht","doi":"10.2174/0115672050364292250113063513","DOIUrl":"https://doi.org/10.2174/0115672050364292250113063513","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is an age-related, progressive neurodegenerative disorder of cognition with clinical features and anatomical hallmarks of amyloid-β plaques and/or neurofibrillary tangles. New studies revealed that microglia, the native immune cells in the brain, are crucial in the development of AD. The present review aims at outlining various roles of microglia in AD especially targeting their role in neuroinflammation. These indicate that microglial dysfunction contributes to AD pathology by affecting both amyloid-β phagocytosis and tau hyperphosphorylation. Other investigative molecular perpetrators, including TREM2, also influence the microglial relevance to amyloid and tau, as well as the overall disease phase. The functional microglia can protect neurons, while the dysfunctional one has the capability of derailing neuronal potentials and aggravating neurodegeneration. We have also discussed therapeutic strategies that start with targeting microglia to reduce neuroinflammation and reinstate balance. However, certain problems, including the side effects of microglial modulation, cost constraint, and accessibility, are areas of concern. In this review, the author presents the current state of knowledge on the potential of microglia-targeted treatments, their risks, and benefits. Thus, this article emphasizes the importance of the expansion of research to decipher the exact manipulation of microglia in AD with the goal of applying these findings given therapeutic approaches.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143461413","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":"Retraction Notice: Optimized Turmeric Extract Reduces β-Amyloid and Phosphorylated Tau Protein Burden in Alzheimer's Transgenic Mice.","authors":"R Douglas Shytle, Jun Tan, Paula C Bickford, Kavon Rezaizadeh, L Hou, Jin Zeng, Paul R Sanberg, Cyndy D Sanberg, Randall S Alberte, Ryan C Fink, Bill Roschek","doi":"10.2174/1567205022999250430120355","DOIUrl":"10.2174/1567205022999250430120355","url":null,"abstract":"<p><p>This article titled \"Optimized Turmeric Extract Reduces β-Amyloid and Phosphorylated Tau Protein Burden in Alzheimer's Transgenic Mice,\" published in Volume 9, Issue 4, 2012 of Current Alzheimer Research (10.2174/156720512800492459 ) has been retracted by the publisher following a thorough investigation that revealed potential data manipulation in the manuscript. As a result, the integrity and validity of the data presented could not be confirmed. The retraction has been made in agreement with the Editor-in-Chief. Despite multiple attempts, the authors did not respond to correspondence regarding this matter. Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. The Bentham Editorial Policy on Retraction can be found at https://benthamscience.com/editorial-policies-main.php BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":"22 2","pages":"e300425241672"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Novel Mitochondrial Dysfunction-Related Alzheimer's Disease Diagnostic Model Using Bioinformatics and Machine Learning.","authors":"Kuo Zhang, Kai Yang, Gongchang Yu, Bin Shi","doi":"10.2174/0115672050353736241218054012","DOIUrl":"https://doi.org/10.2174/0115672050353736241218054012","url":null,"abstract":"<p><p><p> Introduction: Alzheimer's disease (AD) represents the most common neurodegenerative disorder, characterized by progressive cognitive decline and memory loss. Despite the recognition of mitochondrial dysfunction as a critical factor in the pathogenesis of AD, the specific molecular mechanisms remain largely undefined.</p><p><strong>Method: </strong>This study aimed to identify novel biomarkers and therapeutic strategies associated with mitochondrial dysfunction in AD by employing bioinformatics combined with machine learning methodologies. We performed Weighted Gene Co-expression Network Analysis (WGCNA) utilizing gene expression data from the NCBI Gene Expression Omnibus (GEO) database and isolated mitochondria-related genes through the MitoCarta3.0 database. By intersecting WGCNA-derived module genes with identified mitochondrial genes, we compiled a list of 60 mitochondrial dysfunction- related genes (MRGs) significantly enriched in pathways pertinent to mitochondrial function, such as the citrate cycle and oxidative phosphorylation.</p><p><strong>Results: </strong>Employing machine learning techniques, including random forest and LASSO, along with the CytoHubba algorithm, we identified key genes with strong diagnostic potential, such as ACO2, CS, MRPS27, SDHA, SLC25A20, and SYNJ2BP, verified through ROC analysis. Furthermore, an interaction network involving miRNA-MRGs-transcription factors and a protein-drug interaction network revealed potential therapeutic compounds such as Congo red and kynurenic acid that target MRGs.</p><p><strong>Conclusion: </strong>These findings delineate the intricate role of mitochondrial dysfunction in AD and highlight promising avenues for further exploration of biomarkers and therapeutic interventions in this devastating disease.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934318","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":"Quantitative Proteomic Analysis of APP/PS1 Transgenic Mice.","authors":"Jiayuan Wang, Xinyu Wang, Zihui An, Xuan Wang, Yaru Wang, Yuehan Lu, Mengsheng Qiu, Zheqi Liu, Zhou Tan","doi":"10.2174/0115672050345431241113112608","DOIUrl":"https://doi.org/10.2174/0115672050345431241113112608","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a prevalent neurodegenerative disorder affecting the central nervous system (CNS), with its etiology still shrouded in uncertainty. The interplay of extracellular amyloid-β (Aβ) deposition, intracellular neurofibrillary tangles (NFTs) composed of tau protein, cholinergic neuronal impairment, and other pathogenic factors is implicated in the progression of AD.</p><p><strong>Objective: </strong>The current study endeavors to delineate the proteomic landscape alterations in the hippocampus of an AD murine model, utilizing proteomic analysis to identify key physiological and pathological shifts induced by the disease. This endeavor aims to shed light on the underlying pathogenic mechanisms, which could facilitate early diagnosis and pave the way for novel therapeutic interventions for AD.</p><p><strong>Methods: </strong>To dissect the proteomic perturbations induced by Aβ and Presenilin-1 (PS1) in the AD pathogenesis, we undertook a label-free quantitative (LFQ) proteomic analysis focusing on the hippocampal proteome of the APP/PS1 transgenic mouse model. Employing a multi-faceted approach that included differential protein functional enrichment, cluster analysis, and protein-protein interaction (PPI) network analysis, we conducted a comprehensive comparative proteomic study between APP/PS1 transgenic mice and their wild-type C57BL/6 counterparts.</p><p><strong>Results: </strong>Mass spectrometry identified a total of 4817 proteins in the samples, with 2762 proteins being quantifiable. Comparative analysis revealed 396 proteins with differential expression between the APP/PS1 and control groups. Notably, 35 proteins exhibited consistent temporal regulation trends in the hippocampus, with concomitant alterations in biological pathways and PPI networks.</p><p><strong>Conclusions: </strong>This study presents a comparative proteomic profile of transgenic (APP/PS1) and wild-type mice, highlighting the proteomic divergences. Furthermore, it charts the trajectory of proteomic changes in the AD mouse model across the developmental stages from 2 to 12 months, providing insights into the physiological and pathological implications of the disease-associated genetic mutations.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775967","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}