Current Alzheimer research最新文献

{"title":"Alzheimer's Disease and Vascular Dementia, Connecting and Differentiating Features.","authors":"Mikolaj Hurla, Natalia Banaszek, Wojciech Kozubski, Jolanta Dorszewska","doi":"10.2174/0115672050319219240711103459","DOIUrl":"10.2174/0115672050319219240711103459","url":null,"abstract":"<p><p>Alzheimer's disease (AD) and vascular dementia (VD) are the leading causes of dementia, presenting a significant challenge in differential diagnosis. While their clinical presentations can overlap, their underlying pathologies are distinct. AD is characterized by the accumulation of amyloid plaques and neurofibrillary tangles, leading to progressive neurodegeneration. VD, on the other hand, arises from cerebrovascular insults that disrupt blood flow to the brain, causing neuronal injury and cognitive decline. Despite distinct etiologies, AD and VD share common risk factors such as hypertension, diabetes, and hyperlipidemia. Recent research suggests a potential role for oral microbiota in both diseases, warranting further investigation. The diagnostic dilemma lies in the significant overlap of symptoms including memory loss, executive dysfunction, and personality changes. The absence of definitive biomarkers and limitations of current neuroimaging techniques necessitate a multi-modal approach integrating clinical history, cognitive assessment, and neuroimaging findings. Promising avenues for improved diagnosis include the exploration of novel biomarkers like inflammatory markers, MMPs, and circulating microRNAs. Additionally, advanced neuroimaging techniques hold promise in differentiating AD and VD by revealing characteristic cerebrovascular disease patterns and brain atrophy specific to each condition. By elucidating the complexities underlying AD and VD, we can refine diagnostic accuracy and optimize treatment strategies for this ever-growing patient population. Future research efforts should focus on identifying disease-specific biomarkers and developing more effective neuroimaging methods to achieve a definitive diagnosis and guide the development of targeted therapies.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"2-18"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794475","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":"Preface.","authors":"Thomas Van Groen","doi":"10.2174/0115672050409702250506055217","DOIUrl":"10.2174/0115672050409702250506055217","url":null,"abstract":"","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"1"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045728","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":"10.2174/0115672050361661250327061024","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>This review highlights the significant impa","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"123-151"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","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":"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 <i>via</i> 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":"152-163"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","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":"Social Isolation as a Risk Factor for Dementia: Insights from Animal Model Studies.","authors":"Wataru Araki","doi":"10.2174/0115672050373522250421054927","DOIUrl":"10.2174/0115672050373522250421054927","url":null,"abstract":"<p><p>Social isolation (SI) and loneliness (perceived social isolation) are considered as risk factors for developing dementia, including Alzheimer's disease (AD), in the elderly population. Intriguingly, recent reports have shown a significant association of loneliness with a higher amyloid- β (Aβ) burden, suggesting that SI is linked to the pathophysiology of AD. Numerous studies, using rodents or other animal models have revealed diverse biological effects of SI, including induction of oxidative stress and activation of neuroinflammation. Furthermore, using transgenic mouse models of AD, recent investigations have shown that SI affects AD pathology, particularly the deposition of Aβ and neuroinflammation. However, it remains unclarified, by which mechanisms SI confers a significant risk for AD. In this narrative mini-review, I overview published studies on the pathobiological effects of SI in rodent models and discuss the mechanisms by which SI exacerbates AD pathology. Clarification of this issue has significant implications for the design of strategies for preventing cognitive impairment and dementia in the elderly population.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"165-173"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030530","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":"NRN1 may Modulate Tau Phosphorylation and Neuronal Apoptosis in AD <i>via</i> the PIGU-CASP3 Axis.","authors":"Wenshuo Cheng, Jia Zhang, Hui Zhu, Zhenyu Wang, Min Li, Junyi Wang, Hongdan Fu, Yutai Zhang, Yuhang Gao, Changyu Chen, Cunhu Yuan, Jingling Zhu, Jiawei Sun","doi":"10.2174/0115672050361366250328040542","DOIUrl":"10.2174/0115672050361366250328040542","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by hyperphosphorylation of tau protein to form neurofibrillary tangles (NFTs) and amyloid β (Aβ) deposition to form senile plaques, and its specific regulatory mechanism remains incompletely understood. Neurotrophic factors (NTFs) play important roles in neuronal growth, differentiation, and survival, and are considered to have potential therapeutic effects in AD.</p><p><strong>Objective: </strong>This study aimed to investigate the effects of NTFs on tau protein phosphorylation in AD and its underlying mechanisms.</p><p><strong>Methods: </strong>A correlation analysis was conducted between neurotrophic factors and tau protein phosphorylation genes using bioinformatics analysis. The relationship between the candidate neurotrophic factor NRN1 and tau protein phosphorylation was validated <i>in vivo</i>. The effects of NRN1 on tau protein phosphorylation, neural process-related proteins, and apoptosis were explored <i>in vitro</i>. Subsequently, GO and KEGG pathway enrichment analyses and PPI network were utilized to identify potential functions and pathways, as well as pinpoint core regulatory factors. Finally, the mechanism by which NRN1 affects tau protein phosphorylation was explored through Western blot analysis.</p><p><strong>Results: </strong>Bioinformatics analysis revealed a significant negative correlation between NRN1 and MAPT, a gene linked to tau protein phosphorylation. Western blot analysis indicated a decrease in NRN1 expression and an increase in p-tau levels in the hippocampus of AD mice. NRN1 significantly reduced the expression of p-tau in AD cell models and enhanced the expression of MAP2, a protein related to neural processes. Further, apoptosis analysis demonstrated that NRN1 significantly decreased the level of cleaved caspase-3 and elevated the Bcl-2/Bax ratio. Bioinformatics analysis and PPI network construction suggested PIGU and CASP3 to play pivotal roles in NRN1 regulation of tau protein phosphorylation.</p><p><strong>Conclusion: </strong>NRN1 may mitigate tau protein phosphorylation and neuronal apoptosis by modulating the PIGU-CASP3 pathway in AD. This finding offers novel insights into NRN1 as a potential target for the treatment of AD.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"219-231"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060259","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 <i>In Vitro</i> Experiments.","authors":"Chen Li, Yan Chen, Yinhui Yao, Yuxin Zhang, Shu Tong, Yazhen Shang","doi":"10.2174/0115672050376534250310061951","DOIUrl":"10.2174/0115672050376534250310061951","url":null,"abstract":"<p><strong>Aims: </strong>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.</p><p><strong>Methods: </strong>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 <i>in vitro</i> experiments were conducted to verify the molecular expression of NLRP3 in oligodendrocytes within the AD model.</p><p><strong>Results: </strong>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 < 0.05). Additionally, <i>in vitro</i> cell experiments using Reverse transcription quantitative PCR(RT-qPCR), immunofluorescence (IF), and Western blot (WB) analysis confirmed that the expression level of NLRP3 in oligodendrocytes was elevated in the AD model relative to the control group (p < 0.05).</p><p><strong>Conclusion: </strong>This study corroborates the high expression of NLRP3 in AD and its close relationship with the disease through integrated bioinformatics analysis and molecular biology e","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"38-55"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","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":"Relationship between Alzheimer's Disease and Type 2 Diabetes: Critical Review On Cellular and Molecular Common Pathogenic Mechanisms.","authors":"Arantxa Rodriguez-Casado, Mª Isabel Alvarez, Jose-Joaquin Merino, Adolfo Toledano-Díaz, Adolfo Toledano","doi":"10.2174/0115672050375461250325074826","DOIUrl":"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 incidence 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":"92-122"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","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":"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":"164"},"PeriodicalIF":1.9,"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":"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}