Current Alzheimer research最新文献

{"title":"Exploring Potential of Nano-formulations in the Treatment of Alzheimer's Disease through Nasal Route.","authors":"Avinash Tekade, Prasad Kadam, Sachin Jagdale, Samiksha Surwade, Anil Gaikwad, Parth Pawar, Rushikesh Shinde","doi":"10.2174/0115672050290462240222092303","DOIUrl":"https://doi.org/10.2174/0115672050290462240222092303","url":null,"abstract":"<p><strong>Objective: </strong>Alzheimer's disease, a progressive neurodegenerative disorder, severely impacts cognitive function and daily living. The current treatment provides only symptomatic relief, and thus, disease-modifying therapies targeting underlying causes are needed. Although several potential therapies are in various stages of clinical trials, bringing a new Alzheimer's drug to market remains challenging. Hence, researchers are also exploring monoclonal antibodies, tau protein inhibitors, and anti-inflammatory drugs as treatment options. Conventionally designed dosage forms come with limitations like poor absorption, first-pass metabolism, and low bioavailability. They also cause systemic adverse effects because these designed systems do not provide target- specific drug delivery. Thus, in this review, the authors highlighted the current advancements in the development of intranasal nanoformulations for the treatment of Alzheimer's disease. This strategy of delivering anti-Alzheimer drugs through the nasal route may help to target the drug exactly to the brain, achieve rapid onset of action, avoid first-pass metabolism, and reduce the side effects and dose required for administration.</p><p><strong>Conclusion: </strong>Delivering drugs to the brain through the nasal route for treating Alzheimer's disease is crucial due to the limited efficacy of existing treatments and the profound impact of the disease on patients and their families. Thus, by exploring innovative approaches such as nose-to-brain drug delivery, it is possible to improve the quality of life for individuals living with Alzheimer's and alleviate its societal burden.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139998796","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}

{"title":"Exploring the Therapeutic Potential of 8-Prenyldaidzein: A Comprehensive Study of its Multi-Target Efficacy in Alzheimer's Disease.","authors":"Kunal Bhattacharya, Dalakamon Sungoh, Daphilari Kharmujai, Ashraful Islam, Dibyajyoti Das, Saurav Kumar Jha, Nongmaithem Randhoni Chanu, Bhaswati Kashyap, Nilutpal Sharma Bora, Bhargab Jyoti Sahariah, Satyendra Deka, Pukar Khanal","doi":"10.2174/0115672050358848241211080546","DOIUrl":"10.2174/0115672050358848241211080546","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is marked by cognitive decline, amyloid plaques, neurofibrillary tangles, and cholinergic loss. Due to the limited success of amyloid-targeted therapies, attention has shifted to new non-amyloid targets like phosphodiesterases (PDE). This study investigates the potential of <i>Flemingia vestita (FV)</i> phytomolecules and derivatives, particularly 8-Prenyldaidzein, in AD treatment.</p><p><strong>Materials and methods: </strong>Phytocompounds and derivatives were screened for drug-likeness, toxicity, BBB permeability, and ADME profiles. Molecular docking was conducted with PDE5A, BACE-1, and AChE, followed by molecular dynamics (MD) simulations on the best binding complexes.</p><p><strong>Results: </strong>8-Prenyldaidzein, a derivative of daidzein, demonstrated favorable drug-likeness and ADME properties. It exhibited strong binding to PDE5A, BACE-1, and AChE, with MD simulations confirming stable protein-ligand interactions.</p><p><strong>Discussion: </strong>The multi-target potential of 8-Prenyldaidzein, particularly through non-amyloid pathways, offers a promising approach to AD therapy. Its inhibition of PDE5A, BACE-1, and AChE could address multiple aspects of AD pathology.</p><p><strong>Conclusion: </strong>8-Prenyldaidzein shows strong potential as a multi-target inhibitor for AD treatment. While in-silico findings are promising, further experimental validation is needed to confirm its clinical applicability.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"578-598"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884013","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":"Associations between Physical Performance Tests with Cognitive Changes: The Moderating Effect of Cognitive Status.","authors":"Zhi Hao Lim, Junhong Yu, Sangita Kuparasundram, Rathi Mahendran, Ted Kheng Siang Ng","doi":"10.2174/0115672050342857241025091918","DOIUrl":"10.2174/0115672050342857241025091918","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Age-related cognitive decline has been linked with risk factors, including physical performance. Prior studies investigating such associations were typically conducted in clinical settings within Western populations with a frequent focus on late neurocognitive diagnostic stages (i.e., Alzheimer's disease), reducing their generalizability to the Asian population and early neurocognitive stages. To address these knowledge gaps, our study investigated longitudinal associations between physical performance measures at baseline and cognitive change in global cognition, executive functioning (EF) based and non-executive functioning (non- EF) based cognitive domains within the Singaporean population. The moderating role of early neurocognitive status, namely mild cognitive impairment (MCI) and cognitively normal (CN), was also examined.</p><p><strong>Methods: </strong>This paper examined data from 347 participants (CN = 284; MCI = 63) who participated in the Community Health and Intergenerational (CHI) study at baseline and follow-up. Data from a neurocognitive battery and three physical performance tests, namely the timed-up and go (TUG), fast gait speed (FGS) and 30-second chair-stand test (30s-CST), were analysed using multivariate linear regression models.</p><p><strong>Results: </strong>Only one significant association between FGS scores and cognitive change in Semantic Fluency was observed; other associations were not significant. Cognitive status also significantly moderated associations between TUG/30s-CST tasks with several neurocognitive tests.</p><p><strong>Conclusion: </strong>The lack of significant longitudinal associations between baseline physical performance measures and cognitive change differed from findings in the literature. Nevertheless, the moderating role of cognitive status further highlighted the need to account for cognitive status when exploring such associations within a heterogeneous group of older adults without dementia.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"423-436"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690226","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":"Identifying the Role of Oligodendrocyte Genes in the Diagnosis of Alzheimer's Disease through Machine Learning and Bioinformatics Analysis.","authors":"Chen Yan, Li Chen, Yao Yinhui, Shang Yazhen","doi":"10.2174/0115672050338777241028071955","DOIUrl":"10.2174/0115672050338777241028071955","url":null,"abstract":"<p><strong>Background: </strong>Due to the heterogeneity of Alzheimer's disease (AD), the underlying pathogenic mechanisms have not been fully elucidated. Oligodendrocyte (OL) damage and myelin degeneration are prevalent features of AD pathology. When oligodendrocytes are subjected to amyloid-beta (Aβ) toxicity, this damage compromises the structural integrity of myelin and results in a reduction of myelin-associated proteins. Consequently, the impairment of myelin integrity leads to a slowdown or cessation of nerve signal transmission, ultimately contributing to cognitive dysfunction and the progression of AD. Consequently, elucidating the relationship between oligodendrocytes and AD from the perspective of oligodendrocytes is instrumental in advancing our understanding of the pathogenesis of AD.</p><p><strong>Objective: </strong>Here, an attempt is made in this study to identify oligodendrocyte-related biomarkers of AD.</p><p><strong>Methods: </strong>AD datasets were obtained from the Gene Expression Omnibus database and used for consensus clustering to identify subclasses. Hub genes were identified through differentially expressed genes (DEGs) analysis and oligodendrocyte gene set enrichment. Immune infiltration analysis was conducted using the CIBERSORT method. Signature genes were identified using machine learning algorithms and logistic regression. A diagnostic nomogram for predicting AD was developed and validated using external datasets and an AD model. A small molecular compound was identified using the eXtreme Sum algorithm.</p><p><strong>Results: </strong>46 genes were found to be significantly correlated with AD progression by examining the overlap between DEGs and oligodendrocyte genes. Two subclasses of AD, Cluster A, and Cluster B, were identified, and 9 signature genes were identified using a machine learning algorithm to construct a nomogram. Enrichment analysis showed that 9 genes are involved in apoptosis and neuronal development. Immune infiltration analysis found differences in immune cell presence between AD patients and controls. External datasets and RT-qPCR verification showed variation in signature genes between AD patients and controls. Five small molecular compounds were predicted.</p><p><strong>Conclusion: </strong>It was found that 9 oligodendrocyte genes can be used to create a diagnostic tool for AD, which could help in developing new treatments.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"437-455"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592438","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}