Neurodegenerative Diseases最新文献

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Distribution Changes of Neural Precursor Cells in the Brain Stem of Tg(SOD1*G93A)1Gur Mice Tg(SOD1*G93A)1Gur小鼠脑干神经前体细胞的分布变化
IF 3 4区 医学
Neurodegenerative Diseases Pub Date : 2022-05-18 DOI: 10.1159/000525124
Xiaoping Shen, Chunyan Tang, Qin Kang, Yu Zhu, Shengyuan Xu, Jianxiang Jiang, Renshi Xu
{"title":"Distribution Changes of Neural Precursor Cells in the Brain Stem of Tg(SOD1*G93A)1Gur Mice","authors":"Xiaoping Shen, Chunyan Tang, Qin Kang, Yu Zhu, Shengyuan Xu, Jianxiang Jiang, Renshi Xu","doi":"10.1159/000525124","DOIUrl":"https://doi.org/10.1159/000525124","url":null,"abstract":"Objectives: The alteration of vimentin-containing cells (VCCs) proliferation, differentiation, and migration in the brain stem of amyotrophic lateral sclerosis (ALS)-like transgenic mice (Tg(SOD1*G93A)1Gur mice) (TG mice) and wild-type mice (WT mice) at the different disease stages of TG mice was studied in this study. The aims of this study were to investigate the change features of proliferation, differentiation, and migration of endogenous neural precursor cells (NPCs) and to explore the potential effects of NPCs on restoring degenerated neurons in ALS. Methods: The proliferation, differentiation, and migration of VCCs in both different anatomic regions and neural cells of brain stem at the different stages including pre-onset (60–70 days), onset (90–100 days), and progression (120–130 days) stages of TG mice and in WT mice (control) were examined using the immunofluorescence technology. Results: VCCs were mainly distributed in the around (peripheral) central canal (CC) and the nuclei of brain stem in adult WT mice. VCCs proliferated and differentiated into astrocytes and directionally migrated from the around CC to the nuclei of brain stem, and then to the ventral part of damaged regions in brain stem at the pre-onset, onset, and progression stages of TG mice. Conclusions: The data suggest that NPCs widely distributed in the brain stem of adult TG mice can differentiate into astrocytes and migrate into damaged brain regions. This response might be a potential mechanism to repair degenerated motor neurons and restore dysfunctional neural circuitry in ALS.","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"21 1","pages":"132 - 145"},"PeriodicalIF":3.0,"publicationDate":"2022-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48965742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Front & Back Matter 正面和背面事项
IF 3 4区 医学
Neurodegenerative Diseases Pub Date : 2022-04-01 DOI: 10.1159/000524413
P. Unschuld, R. Nitsch
{"title":"Front & Back Matter","authors":"P. Unschuld, R. Nitsch","doi":"10.1159/000524413","DOIUrl":"https://doi.org/10.1159/000524413","url":null,"abstract":"","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"21 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48520941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Plasma Cystatin C Correlates with Plasma NfL Levels and Predicts Disease Progression in Parkinson’s Disease 血浆半胱氨酸蛋白酶抑制剂C与血浆NfL水平相关并预测帕金森病的疾病进展
IF 3 4区 医学
Neurodegenerative Diseases Pub Date : 2022-03-14 DOI: 10.1159/000523982
A. Imarisio, A. Pilotto, E. Garrafa, F. Conforti, S. Masciocchi, R. Turrone, S. Gipponi, E. Cottini, M. Rizzetti, Vanessa Porrini, C. Gussago, M. Pizzi, F. Guadagni, H. Zetterberg, N. Ashton, Abdul Hye, A. Padovani
{"title":"Plasma Cystatin C Correlates with Plasma NfL Levels and Predicts Disease Progression in Parkinson’s Disease","authors":"A. Imarisio, A. Pilotto, E. Garrafa, F. Conforti, S. Masciocchi, R. Turrone, S. Gipponi, E. Cottini, M. Rizzetti, Vanessa Porrini, C. Gussago, M. Pizzi, F. Guadagni, H. Zetterberg, N. Ashton, Abdul Hye, A. Padovani","doi":"10.1159/000523982","DOIUrl":"https://doi.org/10.1159/000523982","url":null,"abstract":"Introduction: Previous studies reported increased plasma levels of cystatin C (Cys-C) in Parkinson’s disease (PD) and claimed for a possible association with disease severity and progression. The aim of this study was to evaluate plasma Cys-C in PD and healthy controls (HC) and test its association with markers of peripheral inflammation, neurodegeneration, and clinical progression in a longitudinal study. Methods: Plasma Cys-C, high-sensitive C-reactive protein, interleukin 6, and neurofilament light chain (NfL) were assessed at the baseline in 71 consecutive non-demented PD and 69 HC. PD patients underwent an extensive motor and cognitive assessment at baseline and after 2 years of follow-up. The association of Cys-C with disease severity was evaluated in a multilinear model adjusted for the effect of age, sex, disease duration, and peripheral inflammation. Results: Cys-C levels appeared to be higher in PD compared to controls and correlated with the plasma neuronal marker NfL (r = 0.204, p = 0.046). In longitudinal analyses, PD patients with higher Cys-C levels exhibited faster motor progression at 2 years of follow-up independently from the peripheral inflammatory profile. Conclusions: Cys-C was associated with higher NfL levels and a remarkably faster motor progression in PD independently from peripheral inflammation. Further studies are needed in order to understand the mechanisms underpinning the association of Cys-C with higher neuronal damage markers in neurodegenerative diseases.","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"21 1","pages":"109 - 116"},"PeriodicalIF":3.0,"publicationDate":"2022-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49131392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Neuroprotective and Therapeutic Effects of Tocovid and Twendee-X on Aβ Oligomer-Induced Damage in the SH-SY5Y Cell Line Tocovid和tweene - x对Aβ寡聚物诱导的SH-SY5Y细胞系损伤的神经保护和治疗作用
IF 3 4区 医学
Neurodegenerative Diseases Pub Date : 2022-03-10 DOI: 10.1159/000523983
Xiao Hu, T. Yamashita, Haibo Yu, Zhihong Bian, Xinran Hu, Tian Feng, Koh Tadokoro, R. Morihara, K. Abe
{"title":"Neuroprotective and Therapeutic Effects of Tocovid and Twendee-X on Aβ Oligomer-Induced Damage in the SH-SY5Y Cell Line","authors":"Xiao Hu, T. Yamashita, Haibo Yu, Zhihong Bian, Xinran Hu, Tian Feng, Koh Tadokoro, R. Morihara, K. Abe","doi":"10.1159/000523983","DOIUrl":"https://doi.org/10.1159/000523983","url":null,"abstract":"Background: Alzheimer’s disease (AD) is the most frequent cause of dementia among the elderly. The accumulation of amyloid beta (Aβ) and its downstream pathological events such as oxidative stress play central roles in AD. Recent studies revealed that Aβ oligomer (AβO)-induced strong neurotoxicity in SH-SY5Y cells via the induction of oxidative stress. Objective: In the present study, we investigated the effect of two antioxidants, Tocovid and Twendee-X, on AβO-induced SH-SY5Y cell damage. Methods: AβOs (2.5 μM) were applied to induce cellular damage in the SH-SY5Y cell line. Cell viability following AβO toxicity, Tau protein phosphorylation, cell morphology, and intracellular reactive oxygen species were assayed with or without different concentrations of Tocovid or Twendee-X. Results: Tocovid (60 μg/mL) and Twendee-X (150 μg/mL) significantly recovered cell viability from AβO toxicity (**p < 0.01, vs. control), attenuated Tau protein phosphorylation (**p < 0.01, vs. AβOs), improved cell morphology (**p < 0.01, vs. AβOs), and suppressed intracellular ROS (**p < 0.01, vs. AβOs) in SH-SY5Y cells. Conclusion: These findings suggest the neuroprotective and therapeutic potential of Tocovid and Twendee-X for AD treatment.","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"21 1","pages":"117 - 125"},"PeriodicalIF":3.0,"publicationDate":"2022-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47824200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 5
Age of Onset and Length of Survival of Queensland Patients with Amyotrophic Lateral Sclerosis: Details of Subjects with Early Onset and Subjects with Long Survival. 昆士兰肌萎缩侧索硬化症患者的发病年龄和生存时间:早期发病和长期生存受试者的详细信息。
IF 3 4区 医学
Neurodegenerative Diseases Pub Date : 2022-01-01 Epub Date: 2022-12-30 DOI: 10.1159/000528875
Robert J Nona, Zhouwei Xu, Gail A Robinson, Robert D Henderson, Pamela A McCombe
{"title":"Age of Onset and Length of Survival of Queensland Patients with Amyotrophic Lateral Sclerosis: Details of Subjects with Early Onset and Subjects with Long Survival.","authors":"Robert J Nona,&nbsp;Zhouwei Xu,&nbsp;Gail A Robinson,&nbsp;Robert D Henderson,&nbsp;Pamela A McCombe","doi":"10.1159/000528875","DOIUrl":"10.1159/000528875","url":null,"abstract":"<p><strong>Introduction: </strong>The aims of the study were to document the characteristics of amyotrophic lateral sclerosis (ALS) patients in Queensland, to examine factors influencing age of onset, and survival, and to study those with early-onset (<45 years) disease and those with long (>5 years) survival.</p><p><strong>Methods: </strong>We studied subjects seen at the ALS Clinic at the Royal Brisbane and Women's Hospital. We recorded sex, age of onset, region of onset, length of survival, presence of family history, type of disease, and evidence of cognitive involvement. We analysed the influence of these features on age of onset and survival. We analysed the features of patients with early onset of disease and patients with long survival.</p><p><strong>Results: </strong>There were 855 ALS patients (505 males) in the cohort. The age of onset was lower in males than females, in patients with a family history of ALS compared to those without, and in patients with spinal onset compared to bulbar onset. Early-onset disease was seen in 10% of patients, and had a greater proportion of males, spinal onset, and classical ALS phenotype compared to late-onset disease. Survival was shorter in females, in patients with bulbar onset, and in patients with classical ALS. Long survival was seen in 18% of patients. Patients with long survival had younger age of onset, greater proportion of males, spinal onset, and fewer patients with classical ALS.</p><p><strong>Conclusion: </strong>Our study confirms that ALS is more prevalent in males and that spinal onset is more common than bulbar onset. Males have earlier onset but longer survival. We found that overall, patients with classical ALS have worse survival than ALS variants, but some patients who were considered to have classical ALS had long survival. This study confirms the similarity of ALS in our region to ALS in other geographical regions.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"104-121"},"PeriodicalIF":3.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10627495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10458930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
New editorship of Neurodegenerative Diseases. 神经退行性疾病的新编辑。
IF 2.6 4区 医学
Neurodegenerative Diseases Pub Date : 2022-01-01 Epub Date: 2023-08-02 DOI: 10.1159/000531607
{"title":"New editorship of Neurodegenerative Diseases.","authors":"","doi":"10.1159/000531607","DOIUrl":"10.1159/000531607","url":null,"abstract":"","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"87"},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9981239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Pivotal Time. 关键时刻。
IF 3 4区 医学
Neurodegenerative Diseases Pub Date : 2022-01-01 Epub Date: 2023-08-03 DOI: 10.1159/000531867
Gilles Allali
{"title":"A Pivotal Time.","authors":"Gilles Allali","doi":"10.1159/000531867","DOIUrl":"10.1159/000531867","url":null,"abstract":"Neurodegenerative Diseases, founded two decades ago by Roger M. Nitsch and Christoph Hock [1], holds a crucial position in filling the gap between fundamental research and clinical applications. It is a great honor to succeed the esteemed founding editors and the accomplished former editor, Paul G. Unschuld, who have elevated the journal to its current level. The field of neurodegenerative diseases is currently experiencing a pivotal time. After the devastating COVID-19 killing countless older adults with neurodegenerative diseases and social isolation being imposed on older survivors, a new disabling condition known as long COVID has emerged, affecting the cognition of young and older adults. Besides the sad consequences of COVID-19, there is a recent hope with the revolutionizing disease-modifying therapies that are becoming available for patients with Alzheimer’s disease (AD). Interestingly, the founder editors of Neurodegenerative Diseasesmade a significant contribution to the development of diseasemodifying therapies for AD [2]. The SARS-CoV-2 pandemic had a worldwide impact (Fig. 1), destabilizing the healthcare systems and leaving a bitter taste as it neglected millions of older adults, particularly those with neurodegenerative diseases, even in the most developed countries, due to the lack of resources and knowledge. In April 2020, I remember evaluating at the Geneva University Hospitals’ ICU during a busy Friday evening a 75-year-old nuclear engineer with Parkinson’s disease, who was struggling with a severe SARS-CoV-2 infection. Remarkably, after 15 days of intubation, he was finally feeling better and able to breathe without respiratory assistance, allowing him the privilege to enjoy the Kiddush of Shabbat, the blessings performed at the beginning of the Friday evening Shabbat dinner; an unusual celebration for an ICU. Prepared with love by his wife, who was unfortunately prohibited from entering to the ICU for “safety” reasons, the patient was slowly eating and gave hope to his son, who stood by his father’s side, reciting together prayers welcoming the Shabbat. It was his last Shabbat. The religious man died 24 h later from a COVID-19 encephalopathy, one of the most devastating neurological complications of COVID19 [3]. On the next Monday, when I shared this sad news with my team, the young neuropsychologist, who had been diligently caring for the patient for 15 days, was totally devastated, falling into a deep burnout. Few months later, the same neuropsychologist experienced a mild SARS-CoV-2 infection but then suffered from a severe long COVID rendering her unable to care for her patients for several months. This story underscores how the pandemic has not only impacted patients and families but has also affected healthcare providers. Numerous reports have highlighted the alarming death rate among healthcare workers, either directly from SARS-CoV-2 infection [4] or from the indirect consequences of overwhelming pressure leading some","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"88-90"},"PeriodicalIF":3.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9934334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ecological Validity of the Montreal Cognitive Assessment in Non-Demented Parkinson's Disease Patients. 蒙特利尔认知评估在非痴呆性帕金森病患者中的生态有效性。
IF 4 4区 医学
Neurodegenerative Diseases Pub Date : 2022-01-01 Epub Date: 2023-07-21 DOI: 10.1159/000532115
Edoardo Nicolò Aiello, Alfonsina D'Iorio, Federica Solca, Silvia Torre, Eleonora Colombo, Alessio Maranzano, Alberto De Lorenzo, Valerio Patisso, Mauro Treddenti, Claudia Morelli, Alberto Doretti, Luca Maderna, Federico Verde, Roberta Ferrucci, Sergio Barbieri, Fabiana Ruggiero, Alberto Priori, Vincenzo Silani, Nicola Ticozzi, Gabriella Santangelo, Andrea Ciammola, Barbara Poletti
{"title":"Ecological Validity of the Montreal Cognitive Assessment in Non-Demented Parkinson's Disease Patients.","authors":"Edoardo Nicolò Aiello, Alfonsina D'Iorio, Federica Solca, Silvia Torre, Eleonora Colombo, Alessio Maranzano, Alberto De Lorenzo, Valerio Patisso, Mauro Treddenti, Claudia Morelli, Alberto Doretti, Luca Maderna, Federico Verde, Roberta Ferrucci, Sergio Barbieri, Fabiana Ruggiero, Alberto Priori, Vincenzo Silani, Nicola Ticozzi, Gabriella Santangelo, Andrea Ciammola, Barbara Poletti","doi":"10.1159/000532115","DOIUrl":"10.1159/000532115","url":null,"abstract":"<p><strong>Background: </strong>The ecological validity of performance-based cognitive screeners needs to be tested in order for them to be fully recommended for use within clinical practice and research.</p><p><strong>Objectives: </strong>The objective of this study was to examine, within an Italian cohort of non-demented Parkinson's disease (PD) patients, the ecological validity of the Montreal Cognitive Assessment (MoCA) by assessing its association with (1) functional independence (FI), (2) quality of life (QoL), and (3) behavioural-psychological (BP) outcomes.</p><p><strong>Methods: </strong>Seventy-four non-demented PD patients were administered the MoCA and underwent motor functional - i.e., Unified Parkinson's Disease Rating Scale (UPDRS), Modified Hoehn-Yahr Scale (HY), and Schwab and England Scale (SES) -, behavioural and psychological - i.e., State- and Trait-Anxiety Inventory-Form Y (STAI-Y1/-Y2), Beck Depression Inventory (BDI), and Dimensional Apathy Scale (DAS) - and QoL evaluations - i.e., MOS 36-Item Short Form Health Survey (SF-36). Associations of interest against FI, QoL, and BP outcomes were tested via Bonferroni-corrected Pearson's/Spearman's correlations while covarying for demographics, disease duration as well as UPDRS-III, UPDRS-IV, and HY scores. Intake of psychotropic drugs was also covaried when assessing the association between the MoCA and BP/QoL measures.</p><p><strong>Results: </strong>MoCA scores were significantly associated with the SES (rs(73) = 0.34; p = 0.005) and the DAS-Executive (r(67) = -0.47; p &lt; 0.001), while not to other FI/BP outcomes and QoL measures.</p><p><strong>Conclusions: </strong>The MoCA is a valid estimate of daily life functional autonomy in non-demented PD patients, also reflecting apathetic features of a dysexecutive nature.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"159-163"},"PeriodicalIF":4.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10216266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CSF Aβ40 and P-Tau181 Might Differentiate Atypical from Typical AD Phenotypes: Preliminary Evidence. CSF a - β40和P-Tau181可能区分非典型和典型AD表型:初步证据
IF 3 4区 医学
Neurodegenerative Diseases Pub Date : 2022-01-01 DOI: 10.1159/000526888
Federico Verde, Edoardo Nicolò Aiello, Eleonora Giacopuzzi Giacopuzzi Grigoli, Ilaria Milone, Antonella Dubini, Antonia Ratti, Barbara Poletti, Nicola Ticozzi, Vincenzo Silani
{"title":"CSF Aβ40 and P-Tau181 Might Differentiate Atypical from Typical AD Phenotypes: Preliminary Evidence.","authors":"Federico Verde,&nbsp;Edoardo Nicolò Aiello,&nbsp;Eleonora Giacopuzzi Giacopuzzi Grigoli,&nbsp;Ilaria Milone,&nbsp;Antonella Dubini,&nbsp;Antonia Ratti,&nbsp;Barbara Poletti,&nbsp;Nicola Ticozzi,&nbsp;Vincenzo Silani","doi":"10.1159/000526888","DOIUrl":"https://doi.org/10.1159/000526888","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed at testing whether CSF levels of amyloid β42 (Aβ42), Aβ40, total tau, and phosphorylated tau (P-tau181) individually contribute to the identification of atypical phenotypes among a retrospective cohort of probable Alzheimer's disease (AD) patients diagnosed by means of the ratio between Aβ42 and Aβ40 (Aβ42/40).</p><p><strong>Methods: </strong>The retrospective study cohort comprised 50 probable AD patients diagnosed by means of the ratio between Aβ42 and Aβ40 (Aβ42/40) and for whom total tau and P-tau181 values were also available. Patients were clinically classified as typical, amnestic-predominant AD (N = 39; 16 males; mean age: 73.4 ± 7.6 years; mean disease duration: 27.4 ± 24.7 months), or atypical phenotypes (N = 11; 6 males; mean age: 70.2 ± 6.5 years; mean disease duration: 35.5 ± 24.9 months) - i.e., posterior cortical atrophy (N = 4), logopenic-variant primary progressive aphasia (N = 4), and behavioural variant AD (N = 3). A logistic regression allowed predicting the occurrence of atypical versus typical phenotypes based on age, sex, and Aβ42, Aβ40, total tau, and P-tau181 levels.</p><p><strong>Results: </strong>Atypical and typical AD patients were comparable for Aβ42/40 values. Only Aβ40 and P-tau181 levels positively (p = 0.015) and negatively (p = 0.019) predicted the occurrence of atypical AD phenotypes, respectively. Classification precision was of 86%, yielding excellent specificity (94.9%) but poor sensitivity (54.5%).</p><p><strong>Conclusions: </strong>The present study delivers promising, albeit preliminary, evidence on the utility of Aβ40 and P-tau181 CSF biomarkers in differentiating atypical from typical Aβ42/40-confirmed AD phenotypes, prompting further research and confirmation on larger cohorts.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"22 2","pages":"83-86"},"PeriodicalIF":3.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9185142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
4-Phthalimidobenzenesulfonamide Derivatives as Acetylcholinesterase and Butyrylcholinesterase Inhibitors: DFTs, 3D-QSAR, ADMET, and Molecular Dynamics Simulation. 4-邻苯二甲酰氨基苯磺酰胺衍生物作为乙酰胆碱酯酶和丁酰胆碱酯酶抑制剂:DFTs、3D-QSAR、ADMET和分子动力学模拟。
IF 3 4区 医学
Neurodegenerative Diseases Pub Date : 2022-01-01 Epub Date: 2022-10-26 DOI: 10.1159/000527516
Syeda Abida Ejaz, Ammara Fayyaz, Hafiz Mohammad Kashif Mahmood, Mubashir Aziz, Syeda Rabia Ejaz, Afrah F Alkhuriji, Wafa Abdullah I Al-Megrin, Abdullahi Tunde Aborode, Gaber El-Saber Batiha
{"title":"4-Phthalimidobenzenesulfonamide Derivatives as Acetylcholinesterase and Butyrylcholinesterase Inhibitors: DFTs, 3D-QSAR, ADMET, and Molecular Dynamics Simulation.","authors":"Syeda Abida Ejaz,&nbsp;Ammara Fayyaz,&nbsp;Hafiz Mohammad Kashif Mahmood,&nbsp;Mubashir Aziz,&nbsp;Syeda Rabia Ejaz,&nbsp;Afrah F Alkhuriji,&nbsp;Wafa Abdullah I Al-Megrin,&nbsp;Abdullahi Tunde Aborode,&nbsp;Gaber El-Saber Batiha","doi":"10.1159/000527516","DOIUrl":"10.1159/000527516","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease is a form of dementia which affects majority of the people. It is characterized by memory loss and other cognitive function disabilities and is one of the most challenging neurodegenerative disorders to treat because of its progressive nature. The disease affects millions of people all around the world, and the number of those affected is expanding every day. In the previous study, the 4-phthalimidobenzenesulfonamide derivatives were synthesized as AChE and BChE inhibitors, and here, we were aiming to further reporting in silico studies of these compounds for efficient drug discovery process and to find out the potential lead compounds.</p><p><strong>Methods: </strong>In silico characterization included density functional theory (DFT) studies, 3D-QSAR, ADMET properties, molecular docking, and molecular dynamic simulations. The geometries of all derivatives were optimized using B3LYP method and 6-311G basis set.</p><p><strong>Results: </strong>The findings of the current study revealed that 4-phthalimidobenzenesulfonamide derivatives exhibited a reactive electronic property which is essential for anticholinesterase activity. Moreover, optimized structures were subjected to molecular docking studies with targeted protein. The compounds 2c and 2g showed excellent binding score of -37.44 and -33.67 kJ/mol with BChE and AChE, respectively, and exhibited strong binding affinity. The potent derivatives produced stable complex with amino acid residues of active pocket of both BChE and AChE. The stability of protein-ligand complexes was determined by molecular dynamic simulation studies, and results were found in correlation with molecular docking findings.</p><p><strong>Conclusion: </strong>Findings of the current study suggested that these derivatives are potent inhibitors of cholinesterase enzyme.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"22 3-4","pages":"122-138"},"PeriodicalIF":3.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41101362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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