scholarly journals Clinical and analytical comparison of three assays for plasma p‐tau isoforms on an ultrasensitive platform

2021 ◽  
Vol 17 (S5) ◽  
Author(s):  
Sherif Bayoumy ◽  
Ben Den Dulk ◽  
Zulaiga Hussainali ◽  
Inge M.W. Verberk ◽  
Wiesje M van der Flier ◽  
...  
2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Sherif Bayoumy ◽  
Inge M. W. Verberk ◽  
Ben den Dulk ◽  
Zulaiga Hussainali ◽  
Marissa Zwan ◽  
...  

Abstract Introduction Studies using different assays and technologies showed highly promising diagnostic value of plasma phosphorylated (P-)tau levels for Alzheimer’s disease (AD). We aimed to compare six P-tau Simoa assays, including three P-tau181 (Eli Lilly, ADx, Quanterix), one P-tau217 (Eli Lilly), and two P-tau231 (ADx, Gothenburg). Methods We studied the analytical (sensitivity, precision, parallelism, dilution linearity, and recovery) and clinical (40 AD dementia patients, age 66±8years, 50%F; 40 age- and sex-matched controls) performance of the assays. Results All assays showed robust analytical performance, and particularly P-tau217 Eli Lilly; P-tau231 Gothenburg and all P-tau181 assays showed robust clinical performance to differentiate AD from controls, with AUCs 0.936–0.995 (P-tau231 ADx: AUC = 0.719). Results obtained with all P-tau181 assays, P-tau217 Eli Lilly assay, and P-tau231 Gothenburg assay strongly correlated (Spearman’s rho > 0.86), while correlations with P-tau231 ADx results were moderate (rho < 0.65). Discussion P-tau isoforms can be measured robustly by several novel high-sensitive Simoa assays.


Author(s):  
حسن أحمد إبراهيم

         الملخّصتحاول هذه الدراسة، التي أحسب أنها الأولى من نوعها، أن تقدم مقارنة تحليلية للإرث الفكري للشيخين محمد عبد الوهاب (1703-1791م) في الجزيرة العربية وشاه ولي الله الدهلوي (1703-1761م) في شبه القارة الهندية في إطار واقعهما البيئي. وتخلص إلى أن لفظ "الوهابية الهندية"، الذي ابتدعه بعض المستشرقين لوصف حركة الإصلاح الإسلامي في الهند، والذي يوحي بأن رائدها الدِّهلوي كان مجرد نسخة مطابقة لمعاصره ابن عبد الوهاب، مصطلح غير دقيق، بل لعله خاطئ كليًّا. وذلك لأن دراسة الإرث الفكري لهذين العملاقين تبين بأنهما أسسا في عصر ما قبل الهجمة الإستعمارية على بلاد المسلمين مدرستين متباينتين من حيث التوجه والمحتوى.الكلمات المفتاحية: محمد عبد الوهاب، شاه ولي الله، الإرث الفكري، التجديد الإسلامي. Abstract          This is the first study to provide an analytical comparison of the intellectual legacy of two great scholars Muhammad ibn ‘Abd al-WahhÉb (1703-1791) in the Arabian Peninsula and Shah WalÊ Allah DehlawÊ (1703-1761) in the Indian sub-continent in the context of their respective environments. It concludes that the term “Indian Wahhabism”, which was coined by some Orientalists to describe the movement for Islamic reform in India, suggesting that Sheikh DehlawÊ was just a duplicate of contemporary Ibn ‘Abd al-WahhÉb, is not only inaccurate but completely incorrect. The study of the intellectual legacy of these two luminaries reveals that they both founded, prior to the pre-colonial attack on the Muslim world, two schools different in terms of orientation and content..Keywords: Muhammad ibn ‘Abd al-WahhÉb, ShÉh WalÊ Allah DehlawÊ, Intellectual Heritage, Islamic Revival.


2021 ◽  
Vol 79 (4) ◽  
pp. 1517-1531
Author(s):  
Alejandra Martínez-Maldonado ◽  
Miguel Ángel Ontiveros-Torres ◽  
Charles R. Harrington ◽  
José Francisco Montiel-Sosa ◽  
Raúl García-Tapia Prandiz ◽  
...  

Background: Alzheimer’s disease (AD) and progressive supranuclear palsy (PSP) are examples of neurodegenerative diseases, characterized by abnormal tau inclusions, that are called tauopathies. AD is characterized by highly insoluble paired helical filaments (PHFs) composed of tau with abnormal post-translational modifications. PSP is a neurodegenerative disease with pathological and clinical heterogeneity. There are six tau isoforms expressed in the adult human brain, with repeated microtubule-binding domains of three (3R) or four (4R) repeats. In AD, the 4R:3R ratio is 1:1. In PSP, the 4R isoform predominates. The lesions in PSP brains contain phosphorylated tau aggregates in both neurons and glial cells. Objective: Our objective was to evaluate and compare the processing of pathological tau in PSP and AD. Methods: Double and triple immunofluorescent labeling with antibodies to specific post-translational tau modifications (phosphorylation, truncation, and conformational changes) and thiazin red (TR) staining were carried out and analyzed by confocal microscopy. Results: Our results showed that PSP was characterized by phosphorylated tau in neurofibrillary tangles (NFTs) and glial cells. Tau truncated at either Glu391 or Asp421 was not observed. Extracellular NFTs (eNFTs) and glial cells in PSP exhibited a strong affinity for TR in the absence of intact or phosphorylated tau. Conclusion: Phosphorylated tau was as abundant in PSP as in AD. The development of eNFTs from both glial cells and neuronal bodies suggests that truncated tau species, different from those observed in AD, could be present in PSP. Additional studies on truncated tau within PSP lesions could improve our understanding of the pathological processing of tau and help identify a discriminatory biomarker for AD and PSP.


2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Jonathan D. Cherry ◽  
Camille D. Esnault ◽  
Zachary H. Baucom ◽  
Yorghos Tripodis ◽  
Bertrand R. Huber ◽  
...  

AbstractChronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease, characterized by hyperphosphorylated tau, found in individuals with a history of exposure to repetitive head impacts. While the neuropathologic hallmark of CTE is found in the cortex, hippocampal tau has proven to be an important neuropathologic feature to examine the extent of disease severity. However, the hippocampus is also heavily affected in many other tauopathies, such as Alzheimer’s disease (AD). How CTE and AD differentially affect the hippocampus is unclear. Using immunofluorescent analysis, a detailed histologic characterization of 3R and 4R tau isoforms and their differential accumulation in the temporal cortex in CTE and AD was performed. CTE and AD were both observed to contain mixed 3R and 4R tau isoforms, with 4R predominating in mild disease and 3R increasing proportionally as pathological severity increased. CTE demonstrated high levels of tau in hippocampal subfields CA2 and CA3 compared to CA1. There were also low levels of tau in the subiculum compared to CA1 in CTE. In contrast, AD had higher levels of tau in CA1 and subiculum compared to CA2/3. Direct comparison of the tau burden between AD and CTE demonstrated that CTE had higher tau densities in CA4 and CA2/3, while AD had elevated tau in the subiculum. Amyloid beta pathology did not contribute to tau isoform levels. Finally, it was demonstrated that higher levels of 3R tau correlated to more severe extracellular tau (ghost tangles) pathology. These findings suggest that mixed 3R/4R tauopathies begin as 4R predominant then transition to 3R predominant as pathological severity increases and ghost tangles develop. Overall, this work demonstrates that the relative deposition of tau isoforms among hippocampal subfields can aid in differential diagnosis of AD and CTE, and might help improve specificity of biomarkers for in vivo diagnosis.


2017 ◽  
Vol 13 (7) ◽  
pp. P205
Author(s):  
Sonia Espindola ◽  
Ana Damianich ◽  
Manuela Sartor ◽  
Juan Belforte ◽  
Jean-Marc Gallo ◽  
...  

1971 ◽  
Vol 93 (4) ◽  
pp. 1113-1119 ◽  
Author(s):  
L. Kops

The concept is developed of analytical comparison between two methods of cutting speed selection when cutting stepped parts: the constant rpm method and constant cutting speed method. Formulas for cost and time of machining stepped parts are derived and analyzed for two different examples of stepped parts: short ones with large differences in diameters (turbine disk) and long ones with small differences in diameters (propeller shaft). The results presented in graphical form show the advisable operating regions for the use of one of the two methods considered. The effect of time required to change the rpm on the effectiveness of the constant speed method is examined and the limit of applicability is determined. It is found that a reduction of as much as 1/3 in cost and time may be obtained when the constant speed method is applied in the case of the turbine disk. It is noted also that the minimum-cost speed and minimum-time speed depend on the choice of the method and on the shape of the machined part as well. The conclusions set out the conditions under which the use of the constant cutting speed method is justified.


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