Current Alzheimer research最新文献

{"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Transgenic Mice,\" published in Volume 9, Issue 4, 2012 of Current Alzheimer Research (10.2174/156720512800492459 ) has been retracted by the publisher following a thorough investigation that revealed potential data manipulation in the manuscript.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}

{"title":"Alzheimer's Disease and Vascular Dementia, Connecting and Differentiating Features.","authors":"Mikołaj Hurła, Natalia Banaszek, Wojciech Kozubski, Jolanta Dorszewska","doi":"10.2174/0115672050319219240711103459","DOIUrl":"https://doi.org/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":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-29","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":"A Look at the Etiology of Alzheimer's Disease based on the Brain Ischemia Model.","authors":"Ryszard Pluta","doi":"10.2174/0115672050320921240627050736","DOIUrl":"10.2174/0115672050320921240627050736","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the frequent form of dementia in the world. Despite over 100 years of research into the causes of AD, including amyloid and tau protein, the research has stalled and has not led to any conclusions. Moreover, numerous projects aimed at finding a cure for AD have also failed to achieve a breakthrough. Thus, the failure of anti-amyloid and anti-tau protein therapy to treat AD significantly influenced the way we began to think about the etiology of the disease. This situation prompted a group of researchers to focus on ischemic brain episodes, which, like AD, mostly present alterations in the hippocampus. In this context, it has been proposed that cerebral ischemic incidents may play a major role in promoting amyloid and tau protein in neurodegeneration in AD. In this review, we summarized the experimental and clinical research conducted over several years on the role of ischemic brain episodes in the development of AD. Studies have shown changes typical of AD in the course of brain neurodegeneration post-ischemia, i.e., progressive brain and hippocampal atrophy, increased amyloid production, and modification of tau protein. In the post-ischemic brain, the diffuse and senile amyloid plaques and the development of neurofibrillary tangles characteristic of AD were revealed. The above data evidently showed that after brain ischemia, there are modifications in protein folding, leading to massive neuronal death and damage to the neuronal network, which triggers dementia with the AD phenotype.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"166-182"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141500104","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":"Advances in Developing Small Molecule Drugs for Alzheimer's Disease.","authors":"Wei Zhang, Liujie Zhang, Mingti Lv, Yun Fu, Xiaowen Meng, Mingyong Wang, Hecheng Wang","doi":"10.2174/0115672050329828240805074938","DOIUrl":"10.2174/0115672050329828240805074938","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the most common type of dementia among middle-aged and elderly individuals. Accelerating the prevention and treatment of AD has become an urgent problem. New technology including Computer-aided drug design (CADD) can effectively reduce the medication cost for patients with AD, reduce the cost of living, and improve the quality of life of patients, providing new ideas for treating AD. This paper reviews the pathogenesis of AD, the latest developments in CADD and other small-molecule docking technologies for drug discovery and development; the current research status of small-molecule compounds for AD at home and abroad from the perspective of drug action targets; the future of AD drug development.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"221-231"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972520","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":"Dysregulation of <i>Porphyromonas gingivalis</i> Agmatine Deiminase Expression in Alzheimer's Disease.","authors":"Asma Hamdi, Sana Baroudi, Alya Gharbi, Wafa Babay, Ahmed Baligh Laaribi, Imene Kacem, Saloua Mrabet, Ines Zidi, Naouel Klibi, Riadh Gouider, Hadda-Imene Ouzari","doi":"10.2174/0115672050327009240808103542","DOIUrl":"10.2174/0115672050327009240808103542","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, with a significant burden on global health. AD is characterized by a progressive cognitive decline and memory loss. Emerging research suggests a potential link between periodontitis, specifically the presence of oral bacteria such as <i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>), and AD progression. <i>P. gingivalis</i> produces an enzyme, Agmatine deiminase (AgD), which converts agmatine to N-carbamoyl putrescine (NCP), serving as a precursor to essential polyamines. Recent studies have confirmed the correlation between disruptions in polyamine metabolism and cognitive impairment.</p><p><strong>Objective: </strong>This study aims to investigate the dysregulation of <i>P. gingivalis</i> Agmatine deiminase (<i>PgAgD</i>) in the context of AD.</p><p><strong>Methods: </strong>Saliva samples were collected from a total of 54 individuals, including 27 AD patients and 27 healthy controls. The expression of the <i>PgAgD</i> gene was analyzed using quantitative Real-- Time PCR.</p><p><strong>Results: </strong>The results showed a significant decrease in <i>PgAgD</i> gene expression in the saliva samples of AD patients compared to healthy controls. This downregulation was found in AD patients with advanced stages of periodontitis. Additionally, a correlation was observed between the decrease in <i>PgAgD</i> expression and the 30-item Mini-Mental State Examination (MMSE) score.</p><p><strong>Conclusion: </strong>These findings suggest that measuring <i>PgAgD</i> expression in saliva could be a noninvasive tool for monitoring AD progression and aid in the early diagnosis of patients with periodontitis. Further research is needed to validate our results and explore the underlying mechanisms linking periodontitis, <i>PgAgD</i> expression, and AD pathophysiology.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"232-241"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141984241","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":"\"Cyclophilin A\" Enzymatic Effect on the Aggregation Behavior of 1N4R Tau Protein: An Overlooked Crucial Determinant that should be Re-considered in Alzheimer's Disease Pathogenesis.","authors":"Samira Ranjbar, Masomeh Mehrabi, Vali Akbari, Somayeh Pashaei, Reza Khodarahmi","doi":"10.2174/0115672050330163240812050223","DOIUrl":"10.2174/0115672050330163240812050223","url":null,"abstract":"<p><strong>Background: </strong>Neurodegenerative disorders like Alzheimer's disease (AD) involve the abnormal aggregation of tau protein, which forms toxic oligomers and amyloid deposits. The structure of tau protein is influenced by the conformational states of distinct proline residues, which are regulated by peptidyl-prolyl isomerases (PPIases). However, there has been no research on the impact of human cyclophilin A (CypA) as a PPIase on (non-phosphorylated) tau protein aggregation.</p><p><strong>Methods: </strong>On the basis of these explanations, we used various spectroscopic techniques to explore the effects of CypA on tau protein aggregation behavior.</p><p><strong>Results: </strong>We demonstrated the role of the isomerization activity of CypA in promoting the formation of tau protein amyloid fibrils with well-defined and highly ordered cross-β structures. According to the \"cistauosis hypothesis,\" CypA's ability to enhance tau protein fibril formation in AD is attributed to the isomerization of specific proline residues from the <i>trans</i> to <i>cis</i> configuration. To corroborate this theory, we conducted refolding experiments using lysozyme as a model protein. The presence of CypA increased lysozyme aggregation and impeded its refolding process. It is known that proper refolding of lysozyme relies on the correct (<i>trans</i>) isomerization of two critical proline residues.</p><p><strong>Conclusion: </strong>Thus, our findings confirmed that CypA induces the <i>trans</i>-to-<i>cis</i> isomerization of specific proline residues, ultimately leading to increased aggregation. Overall, this study highlights the emerging role of isomerization in tau protein pathogenesis in AD.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"242-257"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142006213","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":"Morphometric Analysis of Corpus Callosum in Individuals with Alzheimer's Disease: Magnetic Resonance Imaging (MRI) Study.","authors":"Musa Acar, Sultan Uğur","doi":"10.2174/0115672050335744240820065952","DOIUrl":"10.2174/0115672050335744240820065952","url":null,"abstract":"<p><strong>Introduction: </strong>The Corpus Callosum (CC) is the largest commissural tract in the nervous system. Few studies have examined the extent of CC in Alzheimer's disease (AD) patients, and these studies have reported conflicting findings.</p><p><strong>Materials and methods: </strong>The study was performed using 176 brain MRI images of 88 Alzheimer's patients (55 women-32 men) and 88 healthy individuals (44 women-44 men).</p><p><strong>Results: </strong>In our study, 7 different parameters of the CC were measured, and their average values were determined. We measured each parameter separately in AD patients and healthy individuals and compared them with each other.</p><p><strong>Conclusion: </strong>CC has an important place not only in Patients with AD but also in other neurodegenerative diseases. We consider that our study will be useful in the evaluation of Patients with AD.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"289-294"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142038160","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":"Drive My CAR-AD Research here, there and Everywhere.","authors":"Juan Manuel Górriz Sáez","doi":"10.2174/156720502101240524145811","DOIUrl":"https://doi.org/10.2174/156720502101240524145811","url":null,"abstract":"","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":"21 1","pages":"1-2"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636394","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}