Pub Date : 2024-08-22DOI: 10.2174/0115672050335744240820065952
Musa Acar, Sultan Uğur
Introduction: 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.
Materials and methods: 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).
Results: 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.
Conclusion: 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.
简介胼胝体(CC)是神经系统中最大的神经束。很少有研究对阿尔茨海默病(AD)患者的胼胝体范围进行检查,而且这些研究报告的结果相互矛盾:研究使用了 88 名阿尔茨海默病患者(55 名女性-32 名男性)和 88 名健康人(44 名女性-44 名男性)的 176 张脑核磁共振图像:在我们的研究中,对 CC 的 7 个不同参数进行了测量,并确定了它们的平均值。我们分别测量了注意力缺失症患者和健康人的每个参数,并对它们进行了比较:结论:CC不仅在AD患者中具有重要地位,在其他神经退行性疾病中也同样重要。我们认为,我们的研究将有助于评估 AD 患者。
{"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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-22","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}
Background: 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.
Methods: On the basis of these explanations, we used various spectroscopic techniques to explore the effects of CypA on tau protein aggregation behavior.
Results: 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 trans to cis 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 (trans) isomerization of two critical proline residues.
Conclusion: Thus, our findings confirmed that CypA induces the trans-to-cis 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.
背景:阿尔茨海默病(AD)等神经退行性疾病涉及 tau 蛋白的异常聚集,从而形成有毒的低聚物和淀粉样沉积物。tau 蛋白的结构受不同脯氨酸残基构象状态的影响,而脯氨酸残基构象状态又受肽基-脯氨酰异构酶(PPIases)的调控。然而,目前还没有关于人类环嗜蛋白 A(CypA)作为一种 PPI 酶对(非磷酸化)tau 蛋白聚集的影响的研究:在这些解释的基础上,我们利用各种光谱技术探讨了 CypA 对 tau 蛋白聚集行为的影响:结果:我们证明了CypA的异构化活性在促进tau蛋白淀粉样纤维的形成中的作用,tau蛋白淀粉样纤维具有明确且高度有序的交叉β结构。根据 "cistauosis假说",CypA在AD中促进tau蛋白纤维形成的能力归因于特定脯氨酸残基从反式构型到顺式构型的异构化。为了证实这一理论,我们以溶菌酶为模型蛋白进行了重折叠实验。CypA 的存在增加了溶菌酶的聚集,阻碍了它的重折叠过程。众所周知,溶菌酶的正常重折叠依赖于两个关键脯氨酸残基的正确(反式)异构化:因此,我们的研究结果证实,CypA 会诱导特定脯氨酸残基发生反式-顺式异构化,最终导致聚集增加。总之,这项研究强调了异构化在注意力缺失症 tau 蛋白发病机制中的新作用。
{"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":"https://doi.org/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 trans to cis 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 (trans) isomerization of two critical proline residues.</p><p><strong>Conclusion: </strong>Thus, our findings confirmed that CypA induces the trans-to-cis 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":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-16","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}
Background: 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 Porphyromonas gingivalis (P. gingivalis), and AD progression. P. gingivalis 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.
Objective: This study aims to investigate the dysregulation of P. gingivalis Agmatine deiminase (PgAgD) in the context of AD.
Methods: Saliva samples were collected from a total of 54 individuals, including 27 AD patients and 27 healthy controls. The expression of the PgAgD gene was analyzed using quantitative Real-- Time PCR.
Results: The results showed a significant decrease in PgAgD 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 PgAgD expression and the 30-item Mini-Mental State Examination (MMSE) score.
Conclusion: These findings suggest that measuring PgAgD 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, PgAgD expression, and AD pathophysiology.
背景:阿尔茨海默病(AD)是最普遍的神经退行性疾病,对全球健康造成了重大负担。阿尔茨海默病的特点是认知能力逐渐下降和记忆力减退。新近的研究表明,牙周炎,特别是牙龈卟啉单胞菌(P. gingivalis)等口腔细菌的存在与老年痴呆症的进展之间存在潜在联系。牙龈卟啉单胞菌会产生一种酶,即阿格马丁脱氨酶(AgD),它能将阿格马丁转化为 N-氨基甲酰基腐胺(NCP),作为必需多胺的前体。最近的研究证实了多胺代谢紊乱与认知障碍之间的相关性:本研究旨在探讨在注意力缺失症的背景下牙龈脓疱菌阿加明脱氨酶(PgAgD)的失调情况:方法:共收集了 54 人的唾液样本,其中包括 27 名 AD 患者和 27 名健康对照者。方法:共采集了54人的唾液样本,其中包括27名AD患者和27名健康对照者,采用Real-Time PCR定量分析PgAgD基因的表达:结果表明,与健康对照组相比,AD 患者唾液样本中 PgAgD 基因的表达明显下降。牙周炎晚期的 AD 患者也出现了这种基因表达下调的情况。此外,还观察到 PgAgD 表达的下降与 30 项迷你精神状态检查(MMSE)评分之间存在相关性:这些研究结果表明,测量唾液中 PgAgD 的表达可作为一种非侵入性工具,用于监测 AD 的进展,并有助于牙周炎患者的早期诊断。还需要进一步的研究来验证我们的结果,并探索牙周炎、PgAgD表达和AD病理生理学之间的内在联系。
{"title":"Dysregulation of Porphyromonas gingivalis 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":"https://doi.org/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 Porphyromonas gingivalis (P. gingivalis), and AD progression. P. gingivalis 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 P. gingivalis Agmatine deiminase (PgAgD) 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 PgAgD gene was analyzed using quantitative Real-- Time PCR.</p><p><strong>Results: </strong>The results showed a significant decrease in PgAgD 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 PgAgD expression and the 30-item Mini-Mental State Examination (MMSE) score.</p><p><strong>Conclusion: </strong>These findings suggest that measuring PgAgD 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, PgAgD expression, and AD pathophysiology.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-13","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}
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; and the development trend of new drug development for AD in the future.
{"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":"https://doi.org/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; and the development trend of new drug development for AD in the future.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","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}
Pub Date : 2024-08-12DOI: 10.2174/0115672050333388240801043509
Mohamed T Almeaqli, Yazeed Alaidaa, Faisal M Alnajjar, Abdullah S Al Shararh, Danah S Alharbi, Yazeed I Almslmani, Yousef A Alotibi, Hani S Alrashidi, Wael A Shehri, Hanan M Hassan, Mohammed M H Al-Gayyar
Background: Alzheimer's disease (AD) affects approximately 50 million people globally and is expected to triple by 2050. Arctiin is a lignan found in the Arctium lappa L. plant. Arctiin possesses anti-proliferative, antioxidative and anti-adipogenic.
Objectives: We aimed to explore the potential therapeutic effects of Arctiin on rats with AD by evaluating the expression of TLR4, NLRP3, STAT3, TGF-β, cyclin D1, and CDK2.
Methods: AD was induced in rats by administering 70 mg/kg of aluminum chloride through intraperitoneal injection daily for six weeks. After inducing AD, some rats were treated with 25 mg/kg of Arctiin daily for three weeks through oral gavage. Furthermore, to examine the brain tissue structure, hippocampal sections were stained with hematoxylin/eosin and anti-TLR4 antibodies. The collected samples were analyzed for gene expression and protein levels of TLR4, NLRP3, STAT3, TGF-β, cyclin D1, and CDK2.
Results: In behavioral tests, rats showed a significant improvement in their behavior when treated with Arctiin. Microimages stained with hematoxylin/eosin showed that Arctiin helped to improve the structure and cohesion of the hippocampus, which was previously impaired by AD. Furthermore, Arctiin reduced the expression of TLR4, NLRP3, STAT3, TGF-β, cyclin D1, and CDK2.
Conclusion: Arctiin can enhance rats' behavior and structure of the hippocampus in AD rats. This is achieved through its ability to reduce the expression of both TLR4 and NLRP3, hence inhibiting the inflammasome pathway. Furthermore, Arctiin can improve tissue fibrosis by regulating STAT3 and TGF-β. Lastly, it can block the cell cycle proteins cyclin D1 and CDK2.
{"title":"Therapeutic Effects of Arctiin on Alzheimer's Disease-like Model in Rats by Reducing Oxidative Stress, Inflammasomes and Fibrosis.","authors":"Mohamed T Almeaqli, Yazeed Alaidaa, Faisal M Alnajjar, Abdullah S Al Shararh, Danah S Alharbi, Yazeed I Almslmani, Yousef A Alotibi, Hani S Alrashidi, Wael A Shehri, Hanan M Hassan, Mohammed M H Al-Gayyar","doi":"10.2174/0115672050333388240801043509","DOIUrl":"https://doi.org/10.2174/0115672050333388240801043509","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) affects approximately 50 million people globally and is expected to triple by 2050. Arctiin is a lignan found in the Arctium lappa L. plant. Arctiin possesses anti-proliferative, antioxidative and anti-adipogenic.</p><p><strong>Objectives: </strong>We aimed to explore the potential therapeutic effects of Arctiin on rats with AD by evaluating the expression of TLR4, NLRP3, STAT3, TGF-β, cyclin D1, and CDK2.</p><p><strong>Methods: </strong>AD was induced in rats by administering 70 mg/kg of aluminum chloride through intraperitoneal injection daily for six weeks. After inducing AD, some rats were treated with 25 mg/kg of Arctiin daily for three weeks through oral gavage. Furthermore, to examine the brain tissue structure, hippocampal sections were stained with hematoxylin/eosin and anti-TLR4 antibodies. The collected samples were analyzed for gene expression and protein levels of TLR4, NLRP3, STAT3, TGF-β, cyclin D1, and CDK2.</p><p><strong>Results: </strong>In behavioral tests, rats showed a significant improvement in their behavior when treated with Arctiin. Microimages stained with hematoxylin/eosin showed that Arctiin helped to improve the structure and cohesion of the hippocampus, which was previously impaired by AD. Furthermore, Arctiin reduced the expression of TLR4, NLRP3, STAT3, TGF-β, cyclin D1, and CDK2.</p><p><strong>Conclusion: </strong>Arctiin can enhance rats' behavior and structure of the hippocampus in AD rats. This is achieved through its ability to reduce the expression of both TLR4 and NLRP3, hence inhibiting the inflammasome pathway. Furthermore, Arctiin can improve tissue fibrosis by regulating STAT3 and TGF-β. Lastly, it can block the cell cycle proteins cyclin D1 and CDK2.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972521","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}
Pub Date : 2024-07-29DOI: 10.2174/0115672050319219240711103459
Mikołaj Hurła, Natalia Banaszek, Wojciech Kozubski, Jolanta Dorszewska
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.
阿尔茨海默病(AD)和血管性痴呆(VD)是痴呆症的主要病因,给鉴别诊断带来了巨大挑战。虽然它们的临床表现可能重叠,但其根本病理却截然不同。多发性硬化症的特征是淀粉样蛋白斑块和神经纤维缠结的累积,导致进行性神经变性。而脑血管病则是由于脑血管损伤导致脑血流中断,造成神经元损伤和认知能力下降。尽管病因不同,但注意力缺失症和视网膜病变具有共同的风险因素,如高血压、糖尿病和高脂血症。最近的研究表明,口腔微生物群在这两种疾病中都有潜在作用,值得进一步研究。诊断上的难题在于记忆力减退、执行功能障碍和人格改变等症状的显著重叠。由于缺乏明确的生物标志物,且目前的神经成像技术存在局限性,因此有必要采用多模式方法,将临床病史、认知评估和神经成像结果结合起来。改进诊断的可行途径包括探索新型生物标志物,如炎症标志物、MMPs 和循环 microRNAs。此外,先进的神经影像学技术通过揭示每种疾病特有的脑血管疾病模式和脑萎缩,有望区分出 AD 和 VD。通过阐明 AD 和 VD 背后的复杂性,我们可以提高诊断的准确性,并优化针对这一不断增长的患者群体的治疗策略。未来的研究工作应侧重于确定疾病特异性生物标志物和开发更有效的神经影像学方法,以实现明确诊断并指导靶向疗法的开发。
{"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":null,"pages":null},"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}
Pub Date : 2024-07-22DOI: 10.2174/0115672050309694240708052535
Hatice Yuksel, Elif Bademci Eren, Baris Maldar, Ayse Pinar Titiz
Background: Creutzfeldt-Jakob disease (CJD) is a fatal degenerative brain disease characterized by rapidly progressive dementia. Sporadic CJD (sCJD) is the best-known and most common subtype. Because the disease is uncommon and has highly diverse presenting symptoms, early diagnosis is challenging. We herein report a case of probable sCJD diagnosed at a very early stage.
Case presentation: A 61-year-old female patient had mild attention and memory problems for a few months that were noticed by her husband but did not bother her and did not affect her daily life activities. The first brain magnetic resonance imaging (MRI) at another hospital was normal, lacking diffusion-weighted imaging (DWI). Although the newly taken brain MRI without DWI was normal, the patient's husband brought his patient to our outpatient clinic because he continued to think that there was a difference in his wife's attention and memory. A neurological examination of the patient revealed almost normal findings. The neuropsychiatric evaluation of the patient was consistent with mild cognitive impairment. The patient's electroencephalography taken upon admission had no characteristic findings for CJD but showed generalized epileptiform activity. Therefore, the patient was hospitalized, and a second brain MRI, including DWI sequences, was performed. DWI displayed bilateral asymmetrical typical patterns of restricted diffusion. Cerebrospinal fluid 14-3-3 was positive, and total-tau was highly elevated. She had a diagnosis of probable sCJD at an early stage. Later, the patient developed progressive dementia, ataxia, seizures, and extrapyramidal symptoms, followed by mutism, and died.
Conclusion: Although there is no cure for CJD today, early diagnosis is essential, mainly because of its potential infectivity and for future planning. Diagnosing sCJD in its early stages is difficult. However, taking into account the observations of not only the patient's history but also their longterm partners in cognitive evaluations will be helpful in making an early and accurate diagnosis.
{"title":"The Importance of Long-term Partner Observation in Cognitive Evaluation: A Very Early Creutzfeldt-Jakob Disease in a Patient with Mild Cognitive Impairment.","authors":"Hatice Yuksel, Elif Bademci Eren, Baris Maldar, Ayse Pinar Titiz","doi":"10.2174/0115672050309694240708052535","DOIUrl":"https://doi.org/10.2174/0115672050309694240708052535","url":null,"abstract":"<p><strong>Background: </strong>Creutzfeldt-Jakob disease (CJD) is a fatal degenerative brain disease characterized by rapidly progressive dementia. Sporadic CJD (sCJD) is the best-known and most common subtype. Because the disease is uncommon and has highly diverse presenting symptoms, early diagnosis is challenging. We herein report a case of probable sCJD diagnosed at a very early stage.</p><p><strong>Case presentation: </strong>A 61-year-old female patient had mild attention and memory problems for a few months that were noticed by her husband but did not bother her and did not affect her daily life activities. The first brain magnetic resonance imaging (MRI) at another hospital was normal, lacking diffusion-weighted imaging (DWI). Although the newly taken brain MRI without DWI was normal, the patient's husband brought his patient to our outpatient clinic because he continued to think that there was a difference in his wife's attention and memory. A neurological examination of the patient revealed almost normal findings. The neuropsychiatric evaluation of the patient was consistent with mild cognitive impairment. The patient's electroencephalography taken upon admission had no characteristic findings for CJD but showed generalized epileptiform activity. Therefore, the patient was hospitalized, and a second brain MRI, including DWI sequences, was performed. DWI displayed bilateral asymmetrical typical patterns of restricted diffusion. Cerebrospinal fluid 14-3-3 was positive, and total-tau was highly elevated. She had a diagnosis of probable sCJD at an early stage. Later, the patient developed progressive dementia, ataxia, seizures, and extrapyramidal symptoms, followed by mutism, and died.</p><p><strong>Conclusion: </strong>Although there is no cure for CJD today, early diagnosis is essential, mainly because of its potential infectivity and for future planning. Diagnosing sCJD in its early stages is difficult. However, taking into account the observations of not only the patient's history but also their longterm partners in cognitive evaluations will be helpful in making an early and accurate diagnosis.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750155","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}
Pub Date : 2024-07-22DOI: 10.2174/0115672050314397240708060314
Ming-Zhan Zhang, Yan Sun, Yan-Ming Chen, Fan Guo, Pei-Yang Gao, Lan Tan, Meng-Shan Tan
Object: The study aims to determine whether multimorbidity status is associated with cerebrospinal fluid (CSF) biomarkers for neurodegenerative disorders.
Methods: A total of 827 patients were enrolled from the Parkinson's Progression Markers Initiative (PPMI) database, including 638 patients with early-stage Parkinson's disease (PD) and 189 healthy controls (HCs). Multimorbidity status was evaluated based on the count of long-term conditions (LTCs) and the multimorbidity pattern. Using linear regression models, cross-sectional and longitudinal analyses were conducted to assess the associations of multimorbidity status with CSF biomarkers for neurodegenerative disorders, including α-synuclein (αSyn), amyloid-β42 (Aβ42), total tau (t-tau), phosphorylated tau (p-tau), glial fibrillary acidic protein (GFAP), and neurofilament light chain protein (NfL).
Results: At baseline, the CSF t-tau (p = 0.010), p-tau (p = 0.034), and NfL (p = 0.049) levels showed significant differences across the three categories of LTC counts. In the longitudinal analysis, the presence of LTCs was associated with lower Aβ42 (β < -0.001, p = 0.020), and higher t-tau (β = 0.007, p = 0.026), GFAP (β = 0.013, p = 0.022) and NfL (β = 0.020, p = 0.012); Participants with tumor/musculoskeletal/mental disorders showed higher CSF levels of t-tau (β = 0.016, p = 0.011) and p-tau (β = 0.032, p = 0.044) than those without multimorbidity.
Conclusion: Multimorbidity, especially severe multimorbidity and the pattern of mental/musculoskeletal/ tumor disorders, was associated with CSF biomarkers for neurodegenerative disorders in early-stage PD patients, suggesting that multimorbidity might play a crucial role in aggravating neuronal damage in neurodegenerative diseases.
{"title":"Associations of Multimorbidity with Cerebrospinal Fluid Biomarkers for Neurodegenerative Disorders in Early Parkinson's Disease: A Cross-sectional and Longitudinal Study.","authors":"Ming-Zhan Zhang, Yan Sun, Yan-Ming Chen, Fan Guo, Pei-Yang Gao, Lan Tan, Meng-Shan Tan","doi":"10.2174/0115672050314397240708060314","DOIUrl":"https://doi.org/10.2174/0115672050314397240708060314","url":null,"abstract":"<p><strong>Object: </strong>The study aims to determine whether multimorbidity status is associated with cerebrospinal fluid (CSF) biomarkers for neurodegenerative disorders.</p><p><strong>Methods: </strong>A total of 827 patients were enrolled from the Parkinson's Progression Markers Initiative (PPMI) database, including 638 patients with early-stage Parkinson's disease (PD) and 189 healthy controls (HCs). Multimorbidity status was evaluated based on the count of long-term conditions (LTCs) and the multimorbidity pattern. Using linear regression models, cross-sectional and longitudinal analyses were conducted to assess the associations of multimorbidity status with CSF biomarkers for neurodegenerative disorders, including α-synuclein (αSyn), amyloid-β42 (Aβ42), total tau (t-tau), phosphorylated tau (p-tau), glial fibrillary acidic protein (GFAP), and neurofilament light chain protein (NfL).</p><p><strong>Results: </strong>At baseline, the CSF t-tau (p = 0.010), p-tau (p = 0.034), and NfL (p = 0.049) levels showed significant differences across the three categories of LTC counts. In the longitudinal analysis, the presence of LTCs was associated with lower Aβ42 (β < -0.001, p = 0.020), and higher t-tau (β = 0.007, p = 0.026), GFAP (β = 0.013, p = 0.022) and NfL (β = 0.020, p = 0.012); Participants with tumor/musculoskeletal/mental disorders showed higher CSF levels of t-tau (β = 0.016, p = 0.011) and p-tau (β = 0.032, p = 0.044) than those without multimorbidity.</p><p><strong>Conclusion: </strong>Multimorbidity, especially severe multimorbidity and the pattern of mental/musculoskeletal/ tumor disorders, was associated with CSF biomarkers for neurodegenerative disorders in early-stage PD patients, suggesting that multimorbidity might play a crucial role in aggravating neuronal damage in neurodegenerative diseases.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750154","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}
Pub Date : 2024-07-15DOI: 10.2174/0115672050309014240705113444
Sara Scarfo, Yashar Moshfeghi, William J McGeown
Aim: The aim of the study was to investigate the factors that underpin neuropsychiatric symptoms and how they might evolve over time in people with Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD) dementia.
Background: Neuropsychiatric symptoms are psychiatric and behavioural manifestations that occur in people with AD. These are highly prevalent along the continuum of the disease, including at the stage of MCI, as well as before cognitive decline. Various small- and large-scale projects have investigated the underlying factors that underpin these symptoms; however, the identification of clear clusters is still a matter of debate; furthermore, no study has investigated how the clusters might change across the development of AD pathology by comparing different time points.
Objective: Our objective was to investigate the factors that underpin neuropsychiatric symptoms in Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI) and to assess how the loadings might differ based on considerations such as the disease stage of the samples.
Methods: Data was obtained from the Alzheimer's Disease Neuroimaging Initiative database (adni. loni.usc.edu), using scores from the Neuropsychiatric Inventory, followed up yearly from baseline until month 72. Participant groups included those with MCI or AD dementia, or a mixture of both, with all participants presenting with at least one neuropsychiatric symptom. A series of exploratory Principal Component and Factor (Principal Axis) Analyses were performed using Direct Oblimin rotation.
Results: The best-fitting structure was interpreted for each time point. A consistent, unique structure could not be identified, as the factors were unstable over time, both within the MCI and AD groups. However, some symptoms showed a tendency to load on the same factors across most measurements (i.e., agitation with irritability, depression with anxiety, elation with disinhibition, delusions with hallucinations).
Conclusion: Although the analyses revealed some degree of co-occurrence of neuropsychiatric symptoms across time points/samples, there was also considerable variation. In the AD group, more discrete syndromes were evident at the early time points, whereas a more complex picture of co-occurring symptoms, with differences likely reflecting disease staging, was seen at later time points. As a clear and distinctive factor structure was not consistently identified across time points/ samples, this highlights the potential importance of sample selection (e.g., disease stage and/or heterogeneity) when studying, for example, the neurobiological underpinnings of neuropsychiatric symptoms.
目的:本研究旨在调查轻度认知障碍(MCI)和阿尔茨海默病(AD)痴呆患者神经精神症状的基础因素,以及这些症状如何随时间演变:背景:神经精神症状是阿尔茨海默病患者的精神和行为表现。这些症状在疾病的持续发展过程中非常普遍,包括在 MCI 阶段和认知能力下降之前。各种小型和大型项目都对支撑这些症状的潜在因素进行了调查;然而,如何确定明确的症状群仍然是一个争论不休的问题;此外,还没有研究通过比较不同的时间点来调查这些症状群在 AD 病理发展过程中可能发生的变化:我们的目的是研究阿尔茨海默病(AD)和轻度认知障碍(MCI)中神经精神症状的基础因素,并评估样本的疾病阶段等因素对负载的影响:数据来自阿尔茨海默病神经影像倡议数据库(adni. loni.usc.edu),使用神经精神量表的评分,从基线开始每年随访一次,直至第72个月。参与者群体包括 MCI 或 AD 痴呆症患者,或两者的混合患者,所有参与者都至少有一种神经精神症状。采用直接奥布利明旋转法进行了一系列探索性主成分和因子(主轴)分析:对每个时间点的最佳拟合结构进行了解释。在 MCI 组和 AD 组中,由于因子随时间变化不稳定,因此无法确定一致、独特的结构。然而,在大多数测量中,一些症状显示出在相同因子上加载的趋势(即激动与易怒、抑郁与焦虑、兴奋与抑制、妄想与幻觉):尽管分析表明神经精神症状在不同时间点/样本间存在一定程度的共存性,但也存在相当大的差异。在注意力缺失症群体中,早期时间点的综合征较为分散,而后期时间点的并发症状则更为复杂,其中的差异很可能反映了疾病的分期。由于在不同的时间点/样本中并不能一致地识别出清晰而独特的因子结构,这凸显了样本选择(如疾病分期和/或异质性)在研究神经精神症状的神经生物学基础等方面的潜在重要性。
{"title":"Assessing the Stability of Clusters of Neuropsychiatric Symptoms in Alzheimer's Disease and Mild Cognitive Impairment.","authors":"Sara Scarfo, Yashar Moshfeghi, William J McGeown","doi":"10.2174/0115672050309014240705113444","DOIUrl":"https://doi.org/10.2174/0115672050309014240705113444","url":null,"abstract":"<p><strong>Aim: </strong>The aim of the study was to investigate the factors that underpin neuropsychiatric symptoms and how they might evolve over time in people with Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD) dementia.</p><p><strong>Background: </strong>Neuropsychiatric symptoms are psychiatric and behavioural manifestations that occur in people with AD. These are highly prevalent along the continuum of the disease, including at the stage of MCI, as well as before cognitive decline. Various small- and large-scale projects have investigated the underlying factors that underpin these symptoms; however, the identification of clear clusters is still a matter of debate; furthermore, no study has investigated how the clusters might change across the development of AD pathology by comparing different time points.</p><p><strong>Objective: </strong>Our objective was to investigate the factors that underpin neuropsychiatric symptoms in Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI) and to assess how the loadings might differ based on considerations such as the disease stage of the samples.</p><p><strong>Methods: </strong>Data was obtained from the Alzheimer's Disease Neuroimaging Initiative database (adni. loni.usc.edu), using scores from the Neuropsychiatric Inventory, followed up yearly from baseline until month 72. Participant groups included those with MCI or AD dementia, or a mixture of both, with all participants presenting with at least one neuropsychiatric symptom. A series of exploratory Principal Component and Factor (Principal Axis) Analyses were performed using Direct Oblimin rotation.</p><p><strong>Results: </strong>The best-fitting structure was interpreted for each time point. A consistent, unique structure could not be identified, as the factors were unstable over time, both within the MCI and AD groups. However, some symptoms showed a tendency to load on the same factors across most measurements (i.e., agitation with irritability, depression with anxiety, elation with disinhibition, delusions with hallucinations).</p><p><strong>Conclusion: </strong>Although the analyses revealed some degree of co-occurrence of neuropsychiatric symptoms across time points/samples, there was also considerable variation. In the AD group, more discrete syndromes were evident at the early time points, whereas a more complex picture of co-occurring symptoms, with differences likely reflecting disease staging, was seen at later time points. As a clear and distinctive factor structure was not consistently identified across time points/ samples, this highlights the potential importance of sample selection (e.g., disease stage and/or heterogeneity) when studying, for example, the neurobiological underpinnings of neuropsychiatric symptoms.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636392","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}
Pub Date : 2024-07-15DOI: 10.2174/0115672050323622240705043337
Shikha Kushwah, Ashutosh Mani
Introduction: Alzheimer's disease (AD) is an alarmingly prevalent worldwide neurological disorder that affects millions of people and has severe effects on cognitive functions. The amyloid hypothesis, which links AD to Aβ (amyloid beta) plaque aggregation, is a well-acknowledged theory. The β-secretase (BACE1) is the main cause of Aβ production, which makes it a possible target for therapy. FDA-approved therapies for AD do exist, but none of them explicitly target BACE1, and their effectiveness is constrained and accompanied by adverse effects.
Materials and methods: We determined the essential chemical components of medicinal herbs by conducting a thorough literature research for BACE1. Computational methods like molecular docking, ADMET (Absorption, distribution, metabolism, excretion, toxicity) screening, molecular dynamic simulations, and MMPBSA analysis were performed in order to identify the most promising ligands for β-secretase.
Results: The results suggested that withasomniferol, tinosporide, and curcumin had better binding affinity with BACE1, suggesting their potential as therapeutic candidates against Alzheimer's disease.
Conclusion: Herbal therapeutics have immense applications in the treatment of chronic diseases like Alzheimer's disease, and there is an urgent need to assess their efficacy as therapeutics.
{"title":"Comprehensive Investigation of Natural Ligands as Inhibitors of β Secretase to Identify Alzheimer's Disease Therapeutics.","authors":"Shikha Kushwah, Ashutosh Mani","doi":"10.2174/0115672050323622240705043337","DOIUrl":"https://doi.org/10.2174/0115672050323622240705043337","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease (AD) is an alarmingly prevalent worldwide neurological disorder that affects millions of people and has severe effects on cognitive functions. The amyloid hypothesis, which links AD to Aβ (amyloid beta) plaque aggregation, is a well-acknowledged theory. The β-secretase (BACE1) is the main cause of Aβ production, which makes it a possible target for therapy. FDA-approved therapies for AD do exist, but none of them explicitly target BACE1, and their effectiveness is constrained and accompanied by adverse effects.</p><p><strong>Materials and methods: </strong>We determined the essential chemical components of medicinal herbs by conducting a thorough literature research for BACE1. Computational methods like molecular docking, ADMET (Absorption, distribution, metabolism, excretion, toxicity) screening, molecular dynamic simulations, and MMPBSA analysis were performed in order to identify the most promising ligands for β-secretase.</p><p><strong>Results: </strong>The results suggested that withasomniferol, tinosporide, and curcumin had better binding affinity with BACE1, suggesting their potential as therapeutic candidates against Alzheimer's disease.</p><p><strong>Conclusion: </strong>Herbal therapeutics have immense applications in the treatment of chronic diseases like Alzheimer's disease, and there is an urgent need to assess their efficacy as therapeutics.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636393","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}